Skip to main content

Advertisement

SpringerLink
Log in

Cancer stem cell marker glycosylation: Nature, function and significance

  • Mini-Review
  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

Glycans are essential for the maintenance of normal biological function, with alterations in glycan expression being a hallmark of cancer. Cancer stem cells (CSCs) are a subset of cells within a tumour capable of self-renewal, cellular differentiation and resistances to conventional therapies. As is the case with stem cells, marker proteins present on the cell surface are frequently used to identify and enrich CSCs, with the expression of these markers statistical correlating with the likelihood of cancer recurrence and overall patient survival. As such CSC markers are of high clinical relevance. The majority of markers currently used to identify CSC populations are glycoproteins, and although the diverse biological roles for many of these markers are known, the nature and function of the glycan moiety on these glycoproteins remains to be fully elucidated. This mini-review summarises our current knowledge regarding the types and extent of CSC marker glycosylation, and the various roles that these glycans play in CSC biology, including in mediating cell adhesion, metastasis, evading apoptosis, tear shear resistance, tumour growth, maintaining pluripotency, self-renewal, trafficking, maintaining stability, maintaining enzymatic activity and aiding epithelial mesenchymal transitioning. Given that CSCs markers have multiple diverse biological functions, and are potentially of significant diagnostic and therapeutic benefit the search for new markers that are uniquely expressed on CSCs is vital to selectively target/identify this subset of cancer cells. As such we have also outlined how high-throughput lectin microarrays can be used to successfully profile the glycosylation status of CSC and to identify glyco-markers unique to CSCs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Visvader, J.E., Lindeman, G.J.: Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat. Rev. Cancer. 8, 755–768 (2008)

    Article  CAS  PubMed  Google Scholar 

  2. Reya, T., Morrison, S.J., Clarke, M.F., Weissman, I.L.: Stem cells, cancer, and cancer stem cells. Nat. 414, 105–111 (2001)

    Article  CAS  Google Scholar 

  3. Clarke, M.F., Dick, J.E., Dirks, P.B., Eaves, C.J., Jamieson, C.H., Jones, D.L., Visvader, J., Weissman, I.L., Wahl, G.M.: Cancer stem cells--perspectives on current status and future directions: AACR workshop on cancer stem cells. Cancer res. 66, 9339–9344 (2006)

    Article  CAS  PubMed  Google Scholar 

  4. Griffin, J.D., Lowenberg, B.: Clonogenic cells in acute myeloblastic leukemia. Blood. 68, 1185–1195 (1986)

    CAS  PubMed  Google Scholar 

  5. Park, C.H., Bergsagel, D.E., McCulloch, E.A.: Mouse myeloma tumor stem cells: a primary cell culture assay. J. Natl. Cancer Inst. 46, 411–422 (1971)

    CAS  PubMed  Google Scholar 

  6. Kamel-Reid, S., Dick, J.E.: Engraftment of immune-deficient mice with human hematopoietic stem cells. Sci. 242, 1706–1709 (1988)

    Article  CAS  Google Scholar 

  7. Bonnet, D., Dick, J.E.: Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat. Med. 3, 730–737 (1997)

    Article  CAS  PubMed  Google Scholar 

  8. Singh, A., Settleman, J.: EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene. 29, 4741–4751 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Zhou, B.B., Zhang, H., Damelin, M., Geles, K.G., Grindley, J.C., Dirks, P.B.: Tumour-initiating cells: challenges and opportunities for anticancer drug discovery. Nat. Rev. Drug Discov. 8, 806–823 (2009)

    Article  CAS  PubMed  Google Scholar 

  10. Liu, C., Luo, Y., Liu, X., Lu, P., Zhao, Z.: Clinical implications of CD44+/CD24- tumor cell ratio in breast cancer. Cancer Biother. Radiopharm. 27, 324–328 (2012)

    Article  PubMed  CAS  Google Scholar 

  11. van Rhenen, A., Feller, N., Kelder, A., Westra, A.H., Rombouts, E., Zweegman, S., van der Pol, M.A., Waisfisz, Q., Ossenkoppele, G.J., Schuurhuis, G.J.: High stem cell frequency in acute myeloid leukemia at diagnosis predicts high minimal residual disease and poor survival. Clin. Cancer res. 11, 6520–6527 (2005)

    Article  PubMed  CAS  Google Scholar 

  12. Li, L., Neaves, W.B.: Normal stem cells and cancer stem cells: the niche matters. Cancer res. 66, 4553–4557 (2006)

    Article  CAS  PubMed  Google Scholar 

  13. Beck, B., Blanpain, C.: Unravelling cancer stem cell potential. Nat. Rev. Cancer. 13, 727–738 (2013)

    Article  CAS  PubMed  Google Scholar 

  14. Visvader, J.E.: Cells of origin in cancer. Nat. 469, 314–322 (2011)

    Article  CAS  Google Scholar 

  15. Holczbauer, A., Factor, V.M., Andersen, J.B., Marquardt, J.U., Kleiner, D.E., Raggi, C., Kitade, M., Seo, D., Akita, H., Durkin, M.E., Thorgeirsson, S.S.: Modeling pathogenesis of primary liver cancer in lineage-specific mouse cell types. Gastroenterol. 145, 221–231 (2013)

    Article  CAS  Google Scholar 

  16. Odoux, C., Fohrer, H., Hoppo, T., Guzik, L., Stolz, D.B., Lewis, D.W., Gollin, S.M., Gamblin, T.C., Geller, D.A., Lagasse, E.: A stochastic model for cancer stem cell origin in metastatic colon cancer. Cancer res. 68, 6932–6941 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Springer, G.F., Desai, P.R., Tegtmeyer, H., Carlstedt, S.C., Scanlon, E.F.: T/Tn antigen vaccine is effective and safe in preventing recurrence of advanced human breast-carcinoma. Cancer Biother. 9, 7–15 (1994)

    Article  CAS  PubMed  Google Scholar 

  18. Springer, G.F.: Immunoreactive T and Tn epitopes in cancer diagnosis, prognosis, and immunotherapy. J. Mol. Med. (Berl.) 75(594–602), (1997)

  19. Tsang, J.Y., Huang, Y.H., Luo, M.H., Ni, Y.B., Chan, S.K., Lui, P.C., Yu, A.M., Tan, P.H., Tse, G.M.: Cancer stem cell markers are associated with adverse biomarker profiles and molecular subtypes of breast cancer. Breast Cancer res. Treat. 136, 407–417 (2012)

    Article  CAS  PubMed  Google Scholar 

  20. Diop, N.K., Hrycyna, C.A.: N-linked glycosylation of the human ABC transporter ABCG2 on asparagine 596 is not essential for expression, transport activity, or trafficking to the plasma membrane. Biochemist. 44, 5420–5429 (2005)

    Article  CAS  Google Scholar 

  21. Dean, M.: ABC transporters, drug resistance, and cancer stem cells. J. Mammary Gland Biol. And Neoplasia. 14, 3–9 (2009)

    Article  Google Scholar 

  22. Zeppernick, F., Ahmadi, R., Campos, B., Dictus, C., Helmke, B.M., Becker, N., Lichter, P., Unterberg, A., Radlwimmer, B., Herold-Mende, C.C.: Stem cell marker CD133 affects clinical outcome in glioma patients. Clin. Cancer res. 14, 123–129 (2008)

    Article  CAS  PubMed  Google Scholar 

  23. Cheng, J., Liu, B., Zhang, X.: How powerful is CD133 as a cancer stem cell marker in brain tumors? Cancer Treat. Rev. 35, 403–408 (2009)

    Article  CAS  PubMed  Google Scholar 

  24. Song, W., Li, H., Tao, K., Li, R., Song, Z., Zhao, Q., Zhang, F., Dou, K.: Expression and clinical significance of the stem cell marker CD133 in hepatocellular carcinoma. Int. J. Clin. Pract. 62, 1212–1218 (2008)

    Article  CAS  PubMed  Google Scholar 

  25. Baumann, M., Krause, M.: CD44: a cancer stem cell-related biomarker with predictive potential for radiotherapy. Clin. Cancer res. 16, 5091–5093 (2010)

    Article  CAS  PubMed  Google Scholar 

  26. de Jong, M.C., Pramana, J., van der Wal, J.E., Lacko, M., Peutz-Kootstra, C.J., de Jong, J.M., Takes, R.P., Kaanders, J.H., van der Laan, B.F., Wachters, J., Jansen, J.C., Rasch, C.R., van Velthuysen, M.L., Grenman, R., Hoebers, F.J., Schuuring, E., van den Brekel, M.W., Begg, A.C.: CD44 expression predicts local recurrence after radiotherapy in larynx cancer. Clin. Cancer res. 16, 5329–5238 (2010)

    Article  PubMed  Google Scholar 

  27. Hirata, K., Suzuki, H., Imaeda, H., Matsuzaki, J., Tsugawa, H., Nagano, O., Asakura, K., Saya, H., Hibi, T.: CD44 variant 9 expression in primary early gastric cancer as a predictive marker for recurrence. Br. J. Cancer. 109, 379–386 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Galizia, G., Gemei, M., Del Vecchio, L., Zamboli, A., Di Noto, R., Mirabelli, P., Salvatore, F., Castellano, P., Orditura, M., De Vita, F., Pinto, M., Pignatelli, C., Lieto, E.: Combined CD133/CD44 expression as a prognostic indicator of disease-free survival in patients with colorectal cancer. Arch. Surg. 147, 18–24 (2012)

    Article  CAS  PubMed  Google Scholar 

  29. Ali, H.R., Dawson, S.J., Blows, F.M., Provenzano, E., Pharoah, P.D., Caldas, C.: Cancer stem cell markers in breast cancer: pathological, clinical and prognostic significance. Breast Cancer res. 13, R118 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Gunthert, U., Hofmann, M., Rudy, W., Reber, S., Zoller, M., Haussmann, I., Matzku, S., Wenzel, A., Ponta, H., Herrlich, P.: A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell. 65, 13–24 (1991)

    Article  CAS  PubMed  Google Scholar 

  31. Zoller, M.: CD44: can a cancer-initiating cell profit from an abundantly expressed molecule? Nat. Rev. Cancer. 11, 254–267 (2011)

    Article  PubMed  CAS  Google Scholar 

  32. Takaishi, S., Okumura, T., Tu, S.P., Wang, S.S.W., Shibata, W., Vigneshwaran, R., Gordon, S.A.K., Shimada, Y., Wang, T.C.: Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells. 27, 1006–1020 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhang, S., Balch, C., Chan, M.W., Lai, H.C., Matei, D., Schilder, J.M., Yan, P.S., Huang, T.H., Nephew, K.P.: Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer res. 68, 4311–4320 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Angelastro, J.M., Lame, M.W.: Overexpression of CD133 promotes drug resistance in C6 glioma cells. Mol. Cancer res. 8, 1105–1115 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Tamada, M., Nagano, O., Tateyama, S., Ohmura, M., Yae, T., Ishimoto, T., Sugihara, E., Onishi, N., Yamamoto, T., Yanagawa, H., Suematsu, M., Saya, H.: Modulation of glucose metabolism by CD44 contributes to antioxidant status and drug resistance in cancer cells. Cancer res. 72, 1438–1448 (2012)

    Article  CAS  PubMed  Google Scholar 

  36. Dou, J., Gu, N.: Emerging strategies for the identification and targeting of cancer stem cells. Tumour Biol. 31, 243–253 (2010)

    Article  PubMed  Google Scholar 

  37. Alisson-Silva, F., de Carvalho Rodrigues, D., Vairo, L., Asensi, K.D., Vasconcelos-dos-Santos, A., Mantuano, N.R., Dias, W.B., Rondinelli, E., Goldenberg, R.C., Urmenyi, T.P., Todeschini, A.R.: Evidences for the involvement of cell surface glycans in stem cell pluripotency and differentiation. Glycobiol. 24, 458–468 (2014)

    Article  CAS  Google Scholar 

  38. Reis, C.A., Osorio, H., Silva, L., Gomes, C., David, L.: Alterations in glycosylation as biomarkers for cancer detection. J. Clin. Pathol. 63, 322–329 (2010)

    Article  CAS  PubMed  Google Scholar 

  39. Dennis, J.W., Granovsky, M., Warren, C.E.: Glycoprotein glycosylation and cancer progression. Biochim. Biophys. Acta. 1473, 21–34 (1999)

    Article  CAS  PubMed  Google Scholar 

  40. Hakomori, S.: Glycosylation defining cancer malignancy: new wine in an old bottle. Proc. Natl. Acad. Sci. U. S. a. 99, 10231–10233 (2002)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Pinho, S.S., Reis, C.A.: Glycosylation in cancer: mechanisms and clinical implications. Nat. Rev. Cancer. 15, 540–550 (2015)

    Article  CAS  PubMed  Google Scholar 

  42. Oyelaran, O., Gildersleeve, J.C.: Application of carbohydrate array technology to antigen discovery and vaccine development. Expert rev. Vaccines. 6, 957–969 (2007)

    Article  CAS  PubMed  Google Scholar 

  43. Cheung, S.K.C., Chuang, P.-K., Huang, H.-W., Hwang-Verslues, W.W., Cho, C.H.-H., Yang, W.-B., Shen, C.-N., Hsiao, M., Hsu, T.-L., Chang, C.-F., Wong, C.-H.: Stage-specific embryonic antigen-3 (SSEA-3) and β3GalT5 are cancer specific and significant markers for breast cancer stem cells. Proc. Natl. Acad. Sci. U. S. a. 113, 960–965 (2016)

    Article  CAS  PubMed  Google Scholar 

  44. Adamczyk, B., Tharmalingam, T., Rudd, P.M.: Glycans as cancer biomarkers. Biochim. Biophys. Acta. 1820, 1347–1353 (2012)

    Article  CAS  PubMed  Google Scholar 

  45. Christiansen, M.N., Chik, J., Lee, L., Anugraham, M., Abrahams, J.L., Packer, N.H.: Cell surface protein glycosylation in cancer. Proteom. 14, 525–546 (2014)

    Article  CAS  Google Scholar 

  46. Tucker-Burden, C., Chappa, P., Krishnamoorthy, M., Gerwe, B.A., Scharer, C.D., Heimburg-Molinaro, J., Harris, W., Usta, S.N., Eilertson, C.D., Hadjipanayis, C.G., Stice, S.L., Brat, D.J., Nash, R.J.: Lectins identify glycan biomarkers on glioblastoma-derived cancer stem cells. Stem Cells Dev. 21, 2374–2386 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Liang, Y.J., Ding, Y., Levery, S.B., Lobaton, M., Handa, K., Hakomori, S.I.: Differential Expression Profiles of Glycosphingolipids in Human Breast Cancer Stem Cells Vs. Cancer non-stem Cells. Proc. Natl. Acad. Sci. U. S. a. 110, 4968–4973 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Gupta, V., Bhinge, K.N., Hosain, S.B., Xiong, K., Gu, X., Shi, R., Ho, M.Y., Khoo, K.H., Li, S.C., Li, Y.T., Ambudkar, S.V., Jazwinski, S.M., Liu, Y.Y.: Ceramide glycosylation by glucosylceramide synthase selectively maintains the properties of breast cancer stem cells. J. Biol. Chem. 287, 37195–37205 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Guo, H., Nagy, T., Pierce, M.: Post-translational glycoprotein modifications regulate colon cancer stem cells and colon adenoma progression in Apc(min/+) mice through altered Wnt receptor signaling. J. Biol. Chem. 289, 31534–31549 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Mir, G.H., Helin, J., Skarp, K.P., Cummings, R.D., Makitie, A., Renkonen, R., Leppanen, A.: Glycoforms of human endothelial CD34 that bind L-selectin carry sulfated sialyl Lewis x capped O- and N-glycans. Blood. 114, 733–741 (2009)

    Article  CAS  PubMed Central  Google Scholar 

  51. Furness, S.G., McNagny, K.: Beyond mere markers: functions for CD34 family of sialomucins in hematopoiesis. Immunol. Res. 34, 13–32 (2006)

    Article  CAS  PubMed  Google Scholar 

  52. Drew, E., Merzaban, J.S., Seo, W., Ziltener, H.J., McNagny, K.M.: CD34 and CD43 inhibit mast cell adhesion and are required for optimal mast cell reconstitution. Immun. 22, 43–57 (2005)

    Article  CAS  Google Scholar 

  53. Tifft, C.J., Proia, R.L., Camerini-Otero, R.D.: The folding and cell surface expression of CD4 requires glycosylation. J. Biol. Chem. 267, 3268–3273 (1992)

    CAS  PubMed  Google Scholar 

  54. Lideman, L.F., Gibadulin, R.A.: Dependence of conformation of D3/D4 domains of human CD4 on glycosylation and membrane attachment. Biochem. Mosc. 74(194–200), (2009)

  55. Bui, V.C., Nguyen, T.H.: The role of CD4 on mechanical properties of live cell membrane. J. Biomed. Mater. Res. A. 104, 239–244 (2016)

    Article  PubMed  CAS  Google Scholar 

  56. Leta, E., Roy, A.K., Hou, Z., Jung, L.K.: Production and characterization of the extracellular domain of human CD7 antigen: further evidence that CD7 has a role in T cell signaling. Cell. Immunol. 165, 101–109 (1995)

    Article  CAS  PubMed  Google Scholar 

  57. Stillwell, R., Bierer, B.E.: T cell signal transduction and the role of CD7 in Costimulation. Immunol. Res. 24, 31–52 (2001)

    Article  CAS  PubMed  Google Scholar 

  58. Roberts, A.A., Amano, M., Felten, C., Galvan, M., Sulur, G., Pinter-Brown, L., Dobbeling, U., Burg, G., Said, J., Baum, L.G.: Galectin-1-mediated apoptosis in mycosis fungoides: the roles of CD7 and cell surface glycosylation. Mod. Pathol. 16, 543–551 (2003)

    Article  PubMed  Google Scholar 

  59. Gao, Y., Mehta, K.: N-linked glycosylation of CD38 is required for its structure stabilization but not for membrane localization. Mol. Cell. Biochem. 295, 1–7 (2007)

    Article  CAS  PubMed  Google Scholar 

  60. Chidambaram, N., Chang, C.F.: Functional role of glycosylation on the recombinant CD38/ADP-ribosyl cyclase in CHO cells. Int. J. Biochem. Cell Biol. 30, 1011–1018 (1998)

    Article  CAS  PubMed  Google Scholar 

  61. Vaisitti, T., Aydin, S., Rossi, D., Cottino, F., Bergui, L., D'Arena, G., Bonello, L., Horenstein, A.L., Brennan, P., Pepper, C., Gaidano, G., Malavasi, F., Deaglio, S.: CD38 increases CXCL12-mediated signals and homing of chronic lymphocytic leukemia cells. Leukemia. 24, 958–969 (2010)

    Article  CAS  PubMed  Google Scholar 

  62. Negi, L.M., Talegaonkar, S., Jaggi, M., Ahmad, F.J., Iqbal, Z., Khar, R.K.: Role of CD44 in tumour progression and strategies for targeting. J. Drug Target. 20, 561–573 (2012)

    Article  CAS  PubMed  Google Scholar 

  63. Toole, B.P.: Hyaluronan-CD44 interactions in cancer: paradoxes and possibilities. Clin. Cancer res. 15, 7462–7468 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. English, N.M., Lesley, J.F., Hyman, R.: Site-specific de-N-glycosylation of CD44 can activate hyaluronan binding, and CD44 activation states show distinct threshold densities for hyaluronan binding. Cancer res. 58, 3736–3742 (1998)

    CAS  PubMed  Google Scholar 

  65. Jacobs, P.P., Sackstein, R.: CD44 and HCELL: preventing hematogenous metastasis at step 1. FEBS Lett. 585, 3148–3158 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Munz, M., Fellinger, K., Hofmann, T., Schmitt, B., Gires, O.: Glycosylation is crucial for stability of tumour and cancer stem cell antigen EpCAM. Front. Biosci. 13, 5195–5201 (2008)

    Article  CAS  PubMed  Google Scholar 

  67. Litvinov, S.V., Velders, M.P., Bakker, H.A.M., Fleuren, G.J., Warnaar, S.O.: Ep-cam - a human epithelial antigen is a Homophilic cell-cell adhesion molecule. J. Cell Biol. 125, 437–446 (1994)

    Article  CAS  PubMed  Google Scholar 

  68. Patriarca, C., Macchi, R.M., Marschner, A.K., Mellstedt, H.: Epithelial cell adhesion molecule expression (CD326) in cancer: a short review. Cancer Treat. Rev. 38, 68–75 (2012)

    Article  CAS  PubMed  Google Scholar 

  69. Gao, J., Yan, Q., Wang, J., Liu, S., Yang, X.: Epithelial-to-mesenchymal transition induced by TGF-beta1 is mediated by AP1-dependent EpCAM expression in MCF-7 cells. J. Cell. Physiol. 230, 775–782 (2015)

    Article  CAS  PubMed  Google Scholar 

  70. Shi, M.F., Jiao, J., Lu, W.G., Ye, F., Ma, D., Dong, Q.G., Xie, X.: Identification of cancer stem cell-like cells from human epithelial ovarian carcinoma cell line. Cell. Mol. Life Sci. 67, 3915–3925 (2010)

    Article  CAS  PubMed  Google Scholar 

  71. Aigner, S., Ramos, C.L., Hafezi-Moghadam, A., Lawrence, M.B., Friederichs, J., Altevogt, P., Ley, K.: CD24 mediates rolling of breast carcinoma cells on P-selectin. FASEB j. 12, 1241–1251 (1998)

    CAS  PubMed  Google Scholar 

  72. Bleckmann, C., Geyer, H., Lieberoth, A., Splittstoesser, F., Liu, Y., Feizi, T., Schachner, M., Kleene, R., Reinhold, V., Geyer, R.: O-glycosylation pattern of CD24 from mouse brain. Biol. Chem. 390, 627–645 (2009)

    Article  CAS  PubMed  Google Scholar 

  73. Masson, N.M., Currie, I.S., Terrace, J.D., Garden, O.J., Parks, R.W., Ross, J.A.: Hepatic progenitor cells in human fetal liver express the oval cell marker thy-1. Am. J. Physiol. Gastrointest. Liver Physiol. 291, G45–G54 (2006)

    Article  CAS  PubMed  Google Scholar 

  74. Abkowitz, J.L., Chen, J.: Studies of c-Mpl function distinguish the replication of hematopoietic stem cells from the expansion of differentiating clones. Blood. 109, 5186–5190 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Dong-Feng, Z., Ting, L., Yong, Z., Cheng, C., Xi, Z., Pei-Yan, K.: The TPO/c-MPL pathway in the bone marrow may protect leukemia cells from chemotherapy in AML patients. Pathol. Oncol. Res. 20, 309–317 (2014)

    Article  PubMed  CAS  Google Scholar 

  76. Albu, R.I., Constantinescu, S.N.: Extracellular domain N-glycosylation controls human thrombopoietin receptor cell surface levels. Front. Endocrinol. (Lausanne). 2(1–13), (2011)

  77. Rege, T.A., Hagood, J.S.: Thy-1 as a regulator of cell-cell and cell-matrix interactions in axon regeneration, apoptosis, adhesion, migration, cancer, and fibrosis. FASEB j. 20, 1045–1054 (2006)

    Article  CAS  PubMed  Google Scholar 

  78. Zhou, F., Cui, C., Ge, Y., Chen, H., Li, Q., Yang, Z., Wu, G., Sun, S., Chen, K., Gu, J., Jiang, J., Wei, Y.: Alpha2,3-Sialylation regulates the stability of stem cell marker CD133. J. Biochem. 148, 273–280 (2010)

    Article  CAS  PubMed  Google Scholar 

  79. Kemper, K., Sprick, M.R., de Bree, M., Scopelliti, A., Vermeulen, L., Hoek, M., Zeilstra, J., Pals, S.T., Mehmet, H., Stassi, G., Medema, J.P.: The AC133 epitope, but not the CD133 protein, is lost upon cancer stem cell differentiation. Cancer res. 70, 719–729 (2010)

    Article  CAS  PubMed  Google Scholar 

  80. Bidlingmaier, S., Zhu, X., Liu, B.: The utility and limitations of glycosylated human CD133 epitopes in defining cancer stem cells. J. Mol. Med. (Berl.) 86(1025–1032), (2008)

  81. Huang, S.D., Yuan, Y., Tang, H., Liu, X.H., Fu, C.G., Cheng, H.Z., Bi, J.W., Yu, Y.W., Gong, D.J., Zhang, W., Chen, J., Xu, Z.Y.: Tumor cells positive and negative for the common cancer stem cell markers are capable of initiating tumor growth and generating both progenies. PLoS One. 8, 1–12 (2013)

    CAS  Google Scholar 

  82. Potgens, A.J.G., Schmitz, U., Kaufmann, P., Frank, H.G.: Monoclonal antibody CD133-2 (AC141) against hematopoietic stem cell antigen CD133 shows crossreactivity with cytokeratin 18. J. Histochem. & Cytochem. 50, 1131–1134 (2002)

    Article  CAS  Google Scholar 

  83. Hemmoranta, H., Satomaa, T., Blomqvist, M., Heiskanen, A., Aitio, O., Saarinen, J., Natunen, J., Partanen, J., Laine, J., Jaatinen, T.: N-glycan structures and associated gene expression reflect the characteristic N-glycosylation pattern of human hematopoietic stem and progenitor cells. Exp. Hematol. 35, 1279–1292 (2007)

    Article  CAS  PubMed  Google Scholar 

  84. Elsaba, T.M., Martinez-Pomares, L., Robins, A.R., Crook, S., Seth, R., Jackson, D., McCart, A., Silver, A.R., Tomlinson, I.P., Ilyas, M.: The stem cell marker CD133 associates with enhanced colony formation and cell motility in colorectal cancer. PLoS One. 5, e10714 (2010)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Larzabal, L., El-Nikhely, N., Redrado, M., Seeger, W., Savai, R., Calvo, A.: Differential effects of drugs targeting cancer stem cell (CSC) and non-CSC populations on lung primary tumors and metastasis. PLoS One. 8, e79798 (2013)

    Article  PubMed  PubMed Central  Google Scholar 

  86. Cao, Y., Merling, A., Karsten, U., Goletz, S., Punzel, M., Kraft, R., Butschak, G., Schwartz-Albiez, R.: Expression of CD175 (Tn), CD175s (sialosyl-Tn) and CD176 (Thomsen-Friedenreich antigen) on malignant human hematopoietic cells. Int. J. Cancer. 123, 89–99 (2008)

    Article  CAS  PubMed  Google Scholar 

  87. Yamazaki, H., Xu, C.W., Naito, M., Nishida, H., Okamoto, T., Ghani, F.I., Iwata, S., Inukai, T., Sugita, K., Morimoto, C.: Regulation of cancer stem cell properties by CD9 in human B-acute lymphoblastic leukemia. Biochem. Biophys. Res. Commun. 409, 14–21 (2011)

    Article  CAS  PubMed  Google Scholar 

  88. Heimburg-Molinaro, J., Lum, M., Vijay, G., Jain, M., Almogren, A., Rittenhouse-Olson, K.: Cancer vaccines and carbohydrate epitopes. Vaccine. 29, 8802–8826 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Arndt, N.X., Tiralongo, J., Madge, P.D., von Itzstein, M., Day, C.J.: Differential carbohydrate binding and cell surface glycosylation of human cancer cell lines. J. Cell. Biochem. 112, 2230–2240 (2011)

    Article  CAS  PubMed  Google Scholar 

  90. Pilobello, K.T., Agrawal, P., Rouse, R., Mahal, L.K.: Advances in lectin microarray technology: optimized protocols for piezoelectric print conditions. Curr. Protoc. Chem. Biol. 5, 1–23 (2013)

    PubMed  PubMed Central  Google Scholar 

  91. Ribeiro, J.P., Mahal, L.K.: Dot by dot: analyzing the glycome using lectin microarrays. Curr. Opin. Chem. Biol. 17, 827–831 (2013)

    Article  CAS  PubMed  Google Scholar 

  92. Tao, S.C., Li, Y., Zhou, J., Qian, J., Schnaar, R.L., Zhang, Y., Goldstein, I.J., Zhu, H., Schneck, J.P.: Lectin microarrays identify cell-specific and functionally significant cell surface glycan markers. Glycobiol. 18, 761–769 (2008)

    Article  CAS  Google Scholar 

  93. He, J., Liu, Y., Xie, X., Zhu, T., Soules, M., DiMeco, F., Vescovi, A.L., Fan, X., Lubman, D.M.: Identification of cell surface glycoprotein markers for glioblastoma-derived stem-like cells using a lectin microarray and LC-MS/MS approach. J. Proteome res. 9, 2565–2572 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Schatton, T., Murphy, G.F., Frank, N.Y., Yamaura, K., Waaga-Gasser, A.M., Gasser, M., Zhan, Q., Jordan, S., Duncan, L.M., Weishaupt, C., Fuhlbrigge, R.C., Kupper, T.S., Sayegh, M.H., Frank, M.H.: Identification of cells initiating human melanomas. Nat. 451, 345–349 (2008)

    Article  CAS  Google Scholar 

  95. Lathia, J.D., Gallagher, J., Heddleston, J.M., Wang, J., Eyler, C.E., Macswords, J., Wu, Q., Vasanji, A., McLendon, R.E., Hjelmeland, A.B., Rich, J.N.: Integrin alpha 6 regulates glioblastoma stem cells. Cell Stem Cell. 6, 421–432 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Ginestier, C., Hur, M.H., Charafe-Jauffret, E., Monville, F., Dutcher, J., Brown, M., Jacquemier, J., Viens, P., Kleer, C.G., Liu, S., Schott, A., Hayes, D., Birnbaum, D., Wicha, M.S., Dontu, G.: ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 1, 555–567 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Yang, Z.F., Ngai, P., Ho, D.W., Yu, W.C., Ng, M.N., Lau, C.K., Li, M.L., Tam, K.H., Lam, C.T., Poon, R.T., Fan, S.T.: Identification of local and circulating cancer stem cells in human liver cancer. Hepatol. 47, 919–928 (2008)

    Article  CAS  Google Scholar 

  98. Luo, Y., Nguyen, N., Fujita, M.: Isolation of human melanoma stem cells using ALDH as a marker. Curr. Protoc. Stem Cell Biol. 26, 1–10 (2013)

    Google Scholar 

  99. Yamazaki, H., Nishida, H., Iwata, S., Dang, N.H., Morimoto, C.: CD90 and CD110 correlate with cancer stem cell potentials in human T-acute lymphoblastic leukemia cells. Biochem. Biophys. Res. Commun. 383, 172–177 (2009)

    Article  CAS  PubMed  Google Scholar 

  100. Sullivan, J.P., Spinola, M., Dodge, M., Raso, M.G., Behrens, C., Gao, B., Schuster, K., Shao, C., Larsen, J.E., Sullivan, L.A., Honorio, S., Xie, Y., Scaglioni, P.P., DiMaio, J.M., Gazdar, A.F., Shay, J.W., Wistuba, I.I., Minna, J.D.: Aldehyde dehydrogenase activity selects for lung adenocarcinoma stem cells dependent on notch signaling. Cancer res. 70, 9937–9948 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Bussolati, B., Bruno, S., Grange, C., Ferrando, U., Camussi, G.: Identification of a tumor-initiating stem cell population in human renal carcinomas. FASEB j. 22, 3696–3705 (2008)

    Article  CAS  PubMed  Google Scholar 

  102. Huang, E.H., Hynes, M.J., Zhang, T., Ginestier, C., Dontu, G., Appelman, H., Fields, J.Z., Wicha, M.S., Boman, B.M.: Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer res. 69, 3382–3389 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Li, C., Wu, J.J., Hynes, M., Dosch, J., Sarkar, B., Welling, T.H., di Pasca Magliano, M., Simeone, D.M.: c-Met is a marker of pancreatic cancer stem cells and therapeutic target. Gastroenterol. 141, 2218–2227 (2011)

    Article  CAS  Google Scholar 

  104. Luo, L., Zeng, J., Liang, B., Zhao, Z., Sun, L., Cao, D., Yang, J., Shen, K.: Ovarian cancer cells with the CD117 phenotype are highly tumorigenic and are related to chemotherapy outcome. Exp. Mol. Pathol. 91, 596–602 (2011)

    Article  CAS  PubMed  Google Scholar 

  105. Cox, C.V., Martin, H.M., Kearns, P.R., Virgo, P., Evely, R.S., Blair, A.: Characterization of a progenitor cell population in childhood T-cell acute lymphoblastic leukemia. Blood. 109, 674–682 (2007)

    Article  CAS  PubMed  Google Scholar 

  106. Jin, L., Lee, E.M., Ramshaw, H.S., Busfield, S.J., Peoppl, A.G., Wilkinson, L., Guthridge, M.A., Thomas, D., Barry, E.F., Boyd, A., Gearing, D.P., Vairo, G., Lopez, A.F., Dick, J.E., Lock, R.B.: Monoclonal antibody-mediated targeting of CD123, IL-3 receptor alpha chain, eliminates human acute myeloid leukemic stem cells. Cell Stem Cell. 5, 31–42 (2009)

    Article  CAS  PubMed  Google Scholar 

  107. Shu, Q., Wong, K.K., Su, J.M., Adesina, A.M., Yu, L.T., Tsang, Y.T., Antalffy, B.C., Baxter, P., Perlaky, L., Yang, J., Dauser, R.C., Chintagumpala, M., Blaney, S.M., Lau, C.C., Li, X.N.: Direct orthotopic transplantation of fresh surgical specimen preserves CD133+ tumor cells in clinically relevant mouse models of medulloblastoma and glioma. Stem Cells. 26, 1414–1424 (2008)

    Article  PubMed  Google Scholar 

  108. Nishida, H., Yamazaki, H., Yamada, T., Iwata, S., Dang, N.H., Inukai, T., Sugita, K., Ikeda, Y., Morimoto, C.: CD9 correlates with cancer stem cell potentials in human B-acute lymphoblastic leukemia cells. Biochem. Biophys. Res. Commun. 382, 57–62 (2009)

    Article  CAS  PubMed  Google Scholar 

  109. Ricci-Vitiani, L., Lombardi, D.G., Pilozzi, E., Biffoni, M., Todaro, M., Peschle, C., De Maria, R.: Identification and expansion of human colon-cancer-initiating cells. Nat. 445, 111–115 (2007)

    Article  CAS  Google Scholar 

  110. Fukusumi, T., Ishii, H., Konno, M., Yasui, T., Nakahara, S., Takenaka, Y., Yamamoto, Y., Nishikawa, S., Kano, Y., Ogawa, H., Hasegawa, S., Hamabe, A., Haraguchi, N., Doki, Y., Mori, M., Inohara, H.: CD10 as a novel marker of therapeutic resistance and cancer stem cells in head and neck squamous cell carcinoma. Br. J. Cancer. 111, 506–514 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Shi, C., Tian, R., Wang, M., Wang, X., Jiang, J., Zhang, Z., Li, X., He, Z., Gong, W., Qin, R.: CD44+ CD133+ population exhibits cancer stem cell-like characteristics in human gallbladder carcinoma. Cancer Biol. Ther. 10, 1182–1190 (2010)

    Article  CAS  PubMed  Google Scholar 

  112. Haraguchi, N., Ishii, H., Mimori, K., Tanaka, F., Ohkuma, M., Kim, H.M., Akita, H., Takiuchi, D., Hatano, H., Nagano, H., Barnard, G.F., Doki, Y., Mori, M.: CD13 is a therapeutic target in human liver cancer stem cells. J. Clin. Invest. 120, 3326–3239 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Zhu, Z., Hao, X., Yan, M., Yao, M., Ge, C., Gu, J., Li, J.: Cancer stem/progenitor cells are highly enriched in CD133+CD44+ population in hepatocellular carcinoma. Int. J. Cancer. 126, 2067–2078 (2010)

    Article  CAS  PubMed  Google Scholar 

  114. Son, M.J., Woolard, K., Nam, D.H., Lee, J., Fine, H.A.: SSEA-1 is an enrichment marker for tumor-initiating cells in human glioblastoma. Cell Stem Cell. 4, 440–452 (2009)

    Article  CAS  PubMed  Google Scholar 

  115. Eramo, A., Lotti, F., Sette, G., Pilozzi, E., Biffoni, M., Di Virgilio, A., Conticello, C., Ruco, L., Peschle, C., De Maria, R.: Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ. 15, 504–514 (2008)

    Article  CAS  PubMed  Google Scholar 

  116. Ghosh, N., Matsui, W.: Cancer stem cells in multiple myeloma. Cancer Lett. 277, 1–7 (2009)

    Article  CAS  PubMed  Google Scholar 

  117. Monzania, E., Facchettia, F., Galmozzia, E., Corsinib, E., Benettic, A., Cavazzind, C., Grittid, A., Piccininie, A., Porrof, D., Santinamig, M., Invernicib, G., Paratib, E., Alessandrib, G., Portaa, C.: Melanoma contains CD133 and ABCG2 positive cells with enhanced tumourigenic potential. Cancer res. 43, 935–946 (2007)

    Google Scholar 

  118. Fang, D., Nguyen, T.K., Leishear, K., Finko, R., Kulp, A.N., Hotz, S., Van Belle, P.A., Xu, X., Elder, D.E., Herlyn, M.: A tumorigenic subpopulation with stem cell properties in melanomas. Cancer res. 65, 9328–9337 (2005)

    Article  CAS  PubMed  Google Scholar 

  119. Hermann, P.C., Huber, S.L., Herrler, T., Aicher, A., Ellwart, J.W., Guba, M., Bruns, C.J., Heeschen, C.: Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell. 1, 313–323 (2007)

    Article  CAS  PubMed  Google Scholar 

  120. Al-Hajj, M., Wicha, M.S., Benito-Hernandez, A., Morrison, S.J., Clarke, M.F.: Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. U. S. a. 100, 3983–3988 (2003)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Zhang, W.C., Shyh-Chang, N., Yang, H., Rai, A., Umashankar, S., Ma, S., Soh, B.S., Sun, L.L., Tai, B.C., Nga, M.E., Bhakoo, K.K., Jayapal, S.R., Nichane, M., Yu, Q., Ahmed, D.A., Tan, C., Sing, W.P., Tam, J., Thirugananam, A., Noghabi, M.S., Pang, Y.H., Ang, H.S., Mitchell, W., Robson, P., Kaldis, P., Soo, R.A., Swarup, S., Lim, E.H., Lim, B.: Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. Cell. 148, 259–272 (2012)

    Article  CAS  PubMed  Google Scholar 

  122. Pang, R., Law, W.L., Chu, A.C., Poon, J.T., Lam, C.S., Chow, A.K., Ng, L., Cheung, L.W., Lan, X.R., Lan, H.Y., Tan, V.P., Yau, T.C., Poon, R.T., Wong, B.C.: A subpopulation of CD26+ cancer stem cells with metastatic capacity in human colorectal cancer. Cell Stem Cell. 6, 603–615 (2010)

    Article  CAS  PubMed  Google Scholar 

  123. Gassenmaier, M., Chen, D., Buchner, A., Henkel, L., Schiemann, M., Mack, B., Schendel, D.J., Zimmermann, W., Pohla, H.: CXC chemokine receptor 4 is essential for maintenance of renal cell carcinoma-initiating cells and predicts metastasis. Stem Cells. 31, 1467–1476 (2013)

    Article  CAS  PubMed  Google Scholar 

  124. Boiko, A.D., Razorenova, O.V., van de Rijn, M., Swetter, S.M., Johnson, D.L., Ly, D.P., Butler, P.D., Yang, G.P., Joshua, B., Kaplan, M.J., Longaker, M.T., Weissman, I.L.: Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271. Nat. 466, 133–137 (2010)

    Article  CAS  Google Scholar 

  125. Li, C., Heidt, D.G., Dalerba, P., Burant, C.F., Zhang, L., Adsay, V., Wicha, M., Clarke, M.F., Simeone, D.M.: Identification of pancreatic cancer stem cells. Cancer res. 67, 1030–1037 (2007)

    Article  CAS  PubMed  Google Scholar 

  126. Du, L., Wang, H., He, L., Zhang, J., Ni, B., Wang, X., Jin, H., Cahuzac, N., Mehrpour, M., Lu, Y., Chen, Q.: CD44 is of functional importance for colorectal cancer stem cells. Clin. Cancer res. 14, 6751–6760 (2008)

    Article  CAS  PubMed  Google Scholar 

  127. Clement, V., Sanchez, P., de Tribolet, N., Radovanovic, I., Ruiz i Altaba, A.: HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr. Biol. 17, 165–172 (2007)

    Article  CAS  PubMed  Google Scholar 

  128. Bao, S., Wu, Q., McLendon, R.E., Hao, Y., Shi, Q., Hjelmeland, A.B., Dewhirst, M.W., Bigner, D.D., Rich, J.N.: Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nat. 444, 756–760 (2006)

    Article  CAS  Google Scholar 

  129. Phillips, T.M., McBride, W.H., Pajonk, F.: The response of CD24(−/low)/CD44+ breast cancer-initiating cells to radiation. J. Natl. Cancer Inst. 98, 1777–1785 (2006)

    Article  PubMed  Google Scholar 

  130. Bhatavdekar, J.M., Patel, D.D., Chikhlikar, P.R., Trivedi, T.I., Gosalia, N.M., Ghosh, N., Shah, N.G., Vora, H.H., Suthar, T.P.: Overexpression of CD44: a useful independent predictor of prognosis in patients with colorectal carcinomas. Ann. Surg. Oncol. 5, 495–501 (1998)

    Article  CAS  PubMed  Google Scholar 

  131. Dylla, S.J., Beviglia, L., Park, I.K., Chartier, C., Raval, J., Ngan, L., Pickell, K., Aguilar, J., Lazetic, S., Smith-Berdan, S., Clarke, M.F., Hoey, T., Lewicki, J., Gurney, A.L.: Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS One. 3, e2428 (2008)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Huh, J.W., Kim, H.R., Kim, Y.J., Lee, J.H., Park, Y.S., Cho, S.H., Joo, J.K.: Expression of standard CD44 in human colorectal carcinoma: association with prognosis. Pathol. Int. 59, 241–246 (2009)

    Article  CAS  PubMed  Google Scholar 

  133. Ozawa, M., Ichikawa, Y., Zheng, Y.W., Oshima, T., Miyata, H., Nakazawa, K., Guan, H.B., Shiozawa, M., Akaike, M., Watanabe, K., Ota, M., Fujii, S., Kunisaki, C., Ishikawa, T., Tanaka, K., Akiyama, H., Endo, I., Taniguchi, H.: Prognostic significance of CD44 variant 2 upregulation in colorectal cancer. Br. J. Cancer. 111, 365–374 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Tijink, B.M., Buter, J., de Bree, R., Giaccone, G., Lang, M.S., Staab, A., Leemans, C.R., van Dongen, G.A.: A phase I dose escalation study with anti-CD44v6 bivatuzumab mertansine in patients with incurable squamous cell carcinoma of the head and neck or esophagus. Clin. Cancer res. 12, 6064–6072 (2006)

    Article  CAS  PubMed  Google Scholar 

  135. Lu, J.W., Chang, J.G., Yeh, K.T., Chen, R.M., Tsai, J.J., Hu, R.M.: Overexpression of Thy1/CD90 in human hepatocellular carcinoma is associated with HBV infection and poor prognosis. Acta Histochem. 113, 833–838 (2011)

    Article  CAS  PubMed  Google Scholar 

  136. Piao, L.S., Hur, W., Kim, T.K., Hong, S.W., Kim, S.W., Choi, J.E., Sung, P.S., Song, M.J., Lee, B.C., Hwang, D., Yoon, S.K.: CD133+ liver cancer stem cells modulate radioresistance in human hepatocellular carcinoma. Cancer Lett. 315, 129–137 (2012)

    Article  CAS  PubMed  Google Scholar 

  137. Hou, Y.C., Chao, Y.J., Tung, H.L., Wang, H.C., Shan, Y.S.: Coexpression of CD44-positive/CD133-positive cancer stem cells and CD204-positive tumor-associated macrophages is a predictor of survival in pancreatic ductal adenocarcinoma. Cancer. 120, 2766–2777 (2014)

    Article  CAS  PubMed  Google Scholar 

  138. El-Khattouti, A., Selimovic, D., Haikel, Y., Megahed, M., Gomez, C.R., Hassan, M.: Identification and analysis of CD133(+) melanoma stem-like cells conferring resistance to taxol: an insight into the mechanisms of their resistance and response. Cancer Lett. 343, 123–133 (2014)

    Article  CAS  PubMed  Google Scholar 

  139. Miyabayashi, T., Kagamu, H., Koshio, J., Ichikawa, K., Baba, J., Watanabe, S., Tanaka, H., Tanaka, J., Yoshizawa, H., Nakata, K., Narita, I.: Vaccination with CD133(+) melanoma induces specific Th17 and Th1 cell-mediated antitumor reactivity against parental tumor. Cancer Immunol. Immunother. 60, 1597–1608 (2011)

    Article  PubMed  Google Scholar 

  140. Carr, S.A., Hemling, M.E., Folena-Wasserman, G., Sweet, R.W., Anumula, K., Barr, J.R., Huddleston, M.J., Taylor, P.: Protein and carbohydrate structural analysis of a recombinant soluble CD4 receptor by mass spectrometry. J. Biol. Chem. 264, 21286–21295 (1989)

    CAS  PubMed  Google Scholar 

  141. Chen, R., Jiang, X., Sun, D., Han, G., Wang, F., Ye, M., Wang, L., Zou, H.: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J. Proteome res. 8, 651–661 (2009)

    Article  CAS  PubMed  Google Scholar 

  142. Boucheix, C., Benoit, P., Frachet, P., Billard, M., Worthington, R.E., Gagnon, J., Uzan, G.: Molecular cloning of the CD9 antigen. A new Family of Cell Surface Proteins. J. Biol. Chem. 266, 117–122 (1991)

    CAS  PubMed  Google Scholar 

  143. Sato, B., Katagiri, Y.U., Iijima, K., Yamada, H., Ito, S., Kawasaki, N., Okita, H., Fujimoto, J., Kiyokawa, N.: The human CD10 lacking an N-glycan at Asn(628) is deficient in surface expression and neutral endopeptidase activity. Biochim. Biophys. Acta. 1820, 1715–1723 (2012)

    Article  CAS  PubMed  Google Scholar 

  144. Giatromanolaki, A., Sivridis, E., Fiska, A., Koukourakis, M.I.: The CD44+/CD24- phenotype relates to 'triple-negative' state and unfavorable prognosis in breast cancer patients. Med. Oncol. 28, 745–752 (2011)

    Article  CAS  PubMed  Google Scholar 

  145. Schindelmann, S., Windisch, J., Grundmann, R., Kreienberg, R., Zeillinger, R., Deissler, H.: Expression profiling of mammary carcinoma cell lines: correlation of in vitro invasiveness with expression of CD24. Tumour Biol. 23, 139–145 (2002)

    Article  CAS  PubMed  Google Scholar 

  146. Lanctot, P.M., Gage, F.H., Varki, A.P.: The glycans of stem cells. Curr. Opin. Chem. Biol. 11, 373–380 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Schwartz-Albiez, R., Merling, A., Martin, S., Haas, R., Gross, H.J.: Cell surface sialylation and ecto-sialyltransferase activity of human CD34 progenitors from peripheral blood and bone marrow. Glycoconj. J. 21, 451–459 (2004)

    Article  CAS  PubMed  Google Scholar 

  148. Alessio, M., Roggero, S., Funaro, A., De Monte, L.B., Peruzzi, L., Geuna, M., Malavasi, F.: CD38 molecule: structural and biochemical analysis on human T lymphocytes, thymocytes, and plasma cells. J. Immunol. 145, 878–884 (1990)

    CAS  PubMed  Google Scholar 

  149. Lokeshwar, V.B., Bourguignon, L.Y.: Post-translational protein modification and expression of ankyrin-binding site(s) in GP85 (Pgp-1/CD44) and its biosynthetic precursors during T-lymphoma membrane biosynthesis. J. Biol. Chem. 266, 17983–17989 (1991)

    CAS  PubMed  Google Scholar 

  150. Burdick, M.M., Chu, J.T., Godar, S., Sackstein, R.: HCELL is the major E- and L-selectin ligand expressed on LS174T colon carcinoma cells. J. Biol. Chem. 281, 13899–13905 (2006)

    Article  CAS  PubMed  Google Scholar 

  151. Alves, C.S., Burdick, M.M., Thomas, S.N., Pawar, P., Konstantopoulos, K.: The dual role of CD44 as a functional P-selectin ligand and fibrin receptor in colon carcinoma cell adhesion. Am. J. Physiol. Cell Physiol. 294, C907–C916 (2008)

    Article  CAS  PubMed  Google Scholar 

  152. Napier, S.L., Healy, Z.R., Schnaar, R.L., Konstantopoulos, K.: Selectin ligand expression regulates the initial vascular interactions of colon carcinoma cells: the roles of CD44v and alternative sialofucosylated selectin ligands. J. Biol. Chem. 282, 3433–3441 (2007)

    Article  CAS  PubMed  Google Scholar 

  153. Catterall, J.B., Jones, L.M., Turner, G.A.: Membrane protein glycosylation and CD44 content in the adhesion of human ovarian cancer cells to hyaluronan. Clin. Exp. Metastasis. 17, 583–591 (1999)

    Article  CAS  PubMed  Google Scholar 

  154. Devasahayam, M., Catalino, P.D., Rudd, P.M., Dwek, R.A., Barclay, A.N.: The glycan processing and site occupancy of recombinant thy-1 is markedly affected by the presence of a glycosylphosphatidylinositol anchor. Glycobiol. 9, 1381–1387 (1999)

    Article  CAS  Google Scholar 

  155. Liu, T., Qian, W.J., Gritsenko, M.A., Camp 2nd, D.G., Monroe, M.E., Moore, R.J., Smith, R.D.: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J. Proteome res. 4, 2070–2080 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Brien, C.A., Pollett, A., Gallinger, S., Dick, J.E.: A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nat. 445, 106–110 (2007)

    Article  CAS  Google Scholar 

  157. Shmelkov, S.V., St Clair, R., Lyden, D., Rafii, S.: AC133/CD133/Prominin-1. Int. J. Biochem. Cell Biol. 37, 715–719 (2005)

    Article  CAS  PubMed  Google Scholar 

  158. Chabot, D.J., Chen, H., Dimitrov, D.S., Broder, C.C.: N-linked glycosylation of CXCR4 masks coreceptor function for CCR5-dependent human immunodeficiency virus type 1 isolates. J. Virol. 74, 4404–4413 (2000)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Farzan, M., Babcock, G.J., Vasilieva, N., Wright, P.L., Kiprilov, E., Mirzabekov, T., Choe, H.: The role of post-translational modifications of the CXCR4 amino terminus in stromal-derived factor 1 alpha association and HIV-1 entry. J. Biol. Chem. 277, 29484–29489 (2002)

    Article  CAS  PubMed  Google Scholar 

  160. Meakin, S.O., Shooter, E.M.: Molecular investigations on the high-affinity nerve growth factor receptor. Neuron. 6, 153–163 (1991)

    Article  CAS  PubMed  Google Scholar 

  161. Moitra, K., Scally, M., McGee, K., Lancaster, G., Gold, B., Dean, M.: Molecular evolutionary analysis of ABCB5: the ancestral gene is a full transporter with potentially deleterious single nucleotide polymorphisms. PLoS One. 6, e16318 (2011)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  162. Lassaletta, J.M., Carlsson, K., Garegg, P.J., Schmidt, R.R.: Total synthesis of Sialylgalactosylgloboside: stage-specific embryonic antigen 4. J. Org. Chem. 61, 6873–6880 (1996)

    Article  CAS  PubMed  Google Scholar 

  163. Kannagi, R., Cochran, N.A., Ishigami, F., Hakomori, S., Andrews, P.W., Knowles, B.B., Solter, D.: Stage-specific embryonic antigens (SSEA-3 and -4) are epitopes of a unique globo-series ganglioside isolated from human teratocarcinoma cells. EMBO j. 2, 2355–2361 (1983)

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Glycomics, Gold Coast Campus, Griffith University, Gold Coast, QLD, 4222, Australia

    Brody W. Mallard & Joe Tiralongo

Authors
  1. Brody W. Mallard
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joe Tiralongo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joe Tiralongo.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mallard, B.W., Tiralongo, J. Cancer stem cell marker glycosylation: Nature, function and significance. Glycoconj J 34, 441–452 (2017). https://doi.org/10.1007/s10719-017-9780-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-017-9780-9

Keywords

Search

Navigation