Skip to main content
SpringerLink
Log in

Overview of current standpoints in profiling of circulating tumor cells

  • Review
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

The goal of this review is summarizing current technologies developed as the in vitro prognostic/diagnostic systems that can rapidly separate and detect circulating tumor cells (CTCs) from cancer patient’s blood (1–10 CTCs of 1 billion red blood cells) by labeled and non-labeled method. The review is focused on three major areas of CTC research (1) Summary of previous research on capturing of CTCs, (2) New development of the in vitro prognostic diagnosis system of cancer that is capable of rapid separation of CTCs, (3) Future direction on development of new technologies for CTC profiling. Current CTC researches have helped on identifying patients who may benefit from chemotherapy before treatment, patients who may benefit from continued chemotherapy, and leading to clinical development of CTC-guided chemotherapy strategies. We analyze the feasibility of clinical application of these current CTC research for the ultimate goal of increasing the survivability of cancer patient. The biomolecular assays of viable CTCs from cancer patient may elucidate the mechanism of metastasis and tumor initiating cells and also may have high impact on the development of personalized medicine to overcome the incurable diseases.

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

Scheme 1
Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Alix-Panabieres, C., and K. Pantel. 2013. Circulating tumor cells: liquid biopsy of cancer. Clinical Chemistry 59: 110–118.

    Article  CAS  PubMed  Google Scholar 

  • Arya, S.K., B. Lim, and A.R. Rahman. 2013. Enrichment, detection and clinical significance of circulating tumor cells. Lab on a Chip 13: 1995–2027.

    Article  CAS  PubMed  Google Scholar 

  • Bao, H., P.A. Burke, J. Huang, X. Chen, P.Z. Brohawn, Y. Yao, R.J. Lechleider, R.S. Sikorski, M. Buzoianu, J. Zhang, X. Shi, L.K. Richman, and T.M. Lavallee. 2013. Circulating tumor cells: application as a biomarker for molecular characterization and predictor of survival in an all-comer solid tumor phase I clinical study. PLoS One 8: e58557.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chang, Y.M., M.J. Donovan, and W. Tan. 2013. Using aptamers for cancer biomarker discovery. Journal of Nucleic Acids 2013: 817350.

    Article  PubMed Central  PubMed  Google Scholar 

  • Chun, J.H., H.K. Kim, E. Kim, I.H. Kim, J.H. Kim, H.J. Chang, I.J. Choi, H.S. Lim, I.J. Kim, H.C. Kang, J.H. Park, J.M. Bae, and J.G. Park. 2004. Increased expression of metallothionein is associated with irinotecan resistance in gastric cancer. Cancer Research 64: 4703–4706.

    Article  CAS  PubMed  Google Scholar 

  • Conteduca, V., R. Zamarchi, E. Rossi, V. Condelli, L. Troiani, and M. Aieta. 2013. Circulating tumor cells: utopia or reality? Future Oncology 9: 1337–1352.

    Article  CAS  PubMed  Google Scholar 

  • Dong, Y., A.M. Skelley, K.D. Merdek, K.M. Sprott, C. Jiang, W.E. Pierceall, J. Lin, M. Stocum, W.P. Carney, and D.A. Smirnov. 2013. Microfluidics and circulating tumor cells. The Journal of Molecular Diagnostics 15: 149–157.

    Article  PubMed  Google Scholar 

  • Goncalves, A., B. Esterni, F. Bertucci, R. Sauvan, C. Chabannon, M. Cubizolles, V.J. Bardou, G. Houvenaegel, J. Jacquemier, S. Granjeaud, X.Y. Meng, E.T. Fung, D. Birnbaum, D. Maraninchi, P. Viens, and J.P. Borg. 2006. Postoperative serum proteomic profiles may predict metastatic relapse in high-risk primary breast cancer patients receiving adjuvant chemotherapy. Oncogene 25: 981–989.

    Article  CAS  PubMed  Google Scholar 

  • Hiltermann, T.J., M.M. Pore, A. Van Den Berg, W. Timens, H.M. Boezen, J.J. Liesker, J.H. Schouwink, W.J. Wijnands, G.S. Kerner, F.A. Kruyt, H. Tissing, A.G. Tibbe, L.W. Terstappen, and H.J. Groen. 2012. Circulating tumor cells in small-cell lung cancer: a predictive and prognostic factor. Annals of Oncology 23: 2937–2942.

    Article  CAS  PubMed  Google Scholar 

  • Hosokawa, M., H. Kenmotsu, Y. Koh, T. Yoshino, T. Yoshikawa, T. Naito, T. Takahashi, H. Murakami, Y. Nakamura, A. Tsuya, T. Shukuya, A. Ono, H. Akamatsu, R. Watanabe, S. Ono, K. Mori, H. Kanbara, K. Yamaguchi, T. Tanaka, T. Matsunaga, and N. Yamamoto. 2013. Size-based isolation of circulating tumor cells in lung cancer patients using a microcavity array system. PLoS One 8: e67466.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Huang, T., C.P. Jia, Y. Jun, W.J. Sun, W.T. Wang, H.L. Zhang, H. Cong, F.X. Jing, H.J. Mao, Q.H. Jin, Z. Zhang, Y.J. Chen, G. Li, G.X. Mao, and J.L. Zhao. 2013. Highly sensitive enumeration of circulating tumor cells in lung cancer patients using a size-based filtration microfluidic chip. Biosensors & Bioelectronics 51C: 213–218.

    Google Scholar 

  • Issadore, D., J. Chung, H. Shao, M. Liong, A.A. Ghazani, C.M. Castro, R. Weissleder, and H. Lee. 2012. Ultrasensitive clinical enumeration of rare cells ex vivo using a micro-hall detector. Science Translational Medicine 4: 141ra92.

    Article  PubMed Central  PubMed  Google Scholar 

  • Jiang, Z.F., M. Cristofanilli, Z.M. Shao, Z.S. Tong, E.W. Song, X.J. Wang, N. Liao, X.C. Hu, Y. Liu, Y. Wang, L. Zeng, and M. Zhang. 2013. Circulating tumor cells predict progression-free and overall survival in Chinese patients with metastatic breast cancer, HER2-positive or triple-negative (CBCSG004): a multicenter, double-blind, prospective trial. Annals of Oncology. doi:10.1093/annonc/mdt246.

    Google Scholar 

  • Joo, S., T.D. Chung, and H.C. Kim. 2007. A rapid field-free electroosmotic micropump incorporating charged microchannel surfaces. Sensors and Actuators, B 123: 1161–1168.

    Article  CAS  Google Scholar 

  • Joosse, S.A., and K. Pantel. 2013. Biologic challenges in the detection of circulating tumor cells. Cancer Research 73: 8–11.

    Article  CAS  PubMed  Google Scholar 

  • Kim, H.K., J. Kim, S. Korolevich, I.J. Choi, C.H. Kim, D.J. Munroe, and J.E. Green. 2011. Distinctions in gastric cancer gene expression signatures derived from laser capture microdissection versus histologic macrodissection. BMC Medical Genomics 4: 48.

    Article  PubMed Central  PubMed  Google Scholar 

  • Lianidou, E.S., and A. Markou. 2011. Circulating tumor cells in breast cancer: detection systems, molecular characterization, and future challenges. Clinical Chemistry 57: 1242–1255.

    Article  CAS  PubMed  Google Scholar 

  • Litvinov, S.V., M.P. Velders, HaM Bakker, G.J. Fleuren, and S.O. Warnaar. 1994. Ep-Cam—a human epithelial antigen is a homophilic cell–cell adhesion molecule. Journal of Cell Biology 125: 437–446.

    Article  CAS  PubMed  Google Scholar 

  • Moon, H.S., K. Kwon, S.I. Kim, H. Han, J. Sohn, S. Lee, and H.I. Jung. 2011. Continuous separation of breast cancer cells from blood samples using multi-orifice flow fractionation (MOFF) and dielectrophoresis (DEP). Lab on a Chip 11: 1118–1125.

    Article  CAS  PubMed  Google Scholar 

  • Mostert, B., J. Kraan, J. Bolt-De Vries, P. Van Der Spoel, A.M. Sieuwerts, M. Schutte, A.M. Timmermans, R. Foekens, J.W.M. Martens, J.W. Gratama, J.A. Foekens, and S. Sleijfer. 2011. Detection of circulating tumor cells in breast cancer may improve through enrichment with anti-CD146. Breast Cancer Research and Treatment 127: 33–41.

    Article  CAS  PubMed  Google Scholar 

  • Mostert, B., S. Sleijfer, J.A. Foekens, and J.W. Gratama. 2009. Circulating tumor cells (CTCs): detection methods and their clinical relevance in breast cancer. Cancer Treatment Reviews 35: 463–474.

    Article  CAS  PubMed  Google Scholar 

  • Nagrath, S., L.V. Sequist, S. Maheswaran, D.W. Bell, D. Irimia, L. Ulkus, M.R. Smith, E.L. Kwak, S. Digumarthy, A. Muzikansky, P. Ryan, U.J. Balis, R.G. Tompkins, D.A. Haber, and M. Toner. 2007. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450: 1235–1239.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Osta, W.A., Y. Chen, K. Mikhitarian, M. Mitas, M. Salem, Y.A. Hannun, D.J. Cole, and W.K. Gillanders. 2004. EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy. Cancer Research 64: 5818–5824.

    Article  CAS  PubMed  Google Scholar 

  • Paterlini-Brechot, P., and N.L. Benali. 2007. Circulating tumor cells (CTC) detection: clinical impact and future directions. Cancer Letters 253: 180–204.

    Article  CAS  PubMed  Google Scholar 

  • Punnoose, E.A., S. Atwal, W. Liu, R. Raja, B.M. Fine, B.G. Hughes, R.J. Hicks, G.M. Hampton, L.C. Amler, A. Pirzkall, and M.R. Lackner. 2012. Evaluation of circulating tumor cells and circulating tumor DNA in non-small cell lung cancer: association with clinical endpoints in a phase II clinical trial of pertuzumab and erlotinib. Clinical Cancer Research 18: 2391–2401.

    Article  CAS  PubMed  Google Scholar 

  • Punnoose, E.A., S.K. Atwal, J.M. Spoerke, H. Savage, A. Pandita, R.F. Yeh, A. Pirzkall, B.M. Fine, L.C. Amler, D.S. Chen, and M.R. Lackner. 2010. Molecular biomarker analyses using circulating tumor cells. PLoS One 5: e12517.

    Article  PubMed Central  PubMed  Google Scholar 

  • Spizzo, G., D. Fong, M. Wurm, C. Ensinger, P. Obrist, C. Hofer, G. Mazzoleni, G. Gastl, and P. Went. 2011. EpCAM expression in primary tumour tissues and metastases: an immunohistochemical analysis. Journal of Clinical Pathology 64: 415–420.

    Article  PubMed Central  PubMed  Google Scholar 

  • Stott, S.L., C.H. Hsu, D.I. Tsukrov, M. Yu, D.T. Miyamoto, B.A. Waltman, S.M. Rothenberg, A.M. Shah, M.E. Smas, G.K. Korir, F.P. Floyd, A.J. Gilman, J.B. Lord, D. Winokur, S. Springer, D. Irimia, S. Nagrath, L.V. Sequist, R.J. Lee, K.J. Isselbacher, S. Maheswaran, D.A. Haber, and M. Toner. 2010a. Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. Proceedings of the National Academy of Sciences of the United States of America 107: 18392–18397.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Stott, S.L., R.J. Lee, S. Nagrath, M. Yu, D.T. Miyamoto, L. Ulkus, E.J. Inserra, M. Ulman, S. Springer, Z. Nakamura, A.L. Moore, D.I. Tsukrov, M.E. Kempner, D.M. Dahl, C.L. Wu, A.J. Iafrate, M.R. Smith, R.G. Tompkins, L.V. Sequist, M. Toner, D.A. Haber, and S. Maheswaran. 2010b. Isolation and characterization of circulating tumor cells from patients with localized and metastatic prostate cancer. Science Translational Medicine 2: 25ra23.

    Article  PubMed Central  PubMed  Google Scholar 

  • Takano, M., Y. Kikuchi, T. Asakawa, T. Goto, T. Kita, K. Kudoh, J. Kigawa, N. Sakuragi, M. Sakamoto, T. Sugiyama, N. Yaegashi, H. Tsuda, H. Seto, and M. Shiwa. 2010. Identification of potential serum markers for endometrial cancer using protein expression profiling. Journal of Cancer Research and Clinical Oncology 136: 475–481.

    Article  CAS  PubMed  Google Scholar 

  • Takano, S., H. Yoshitomi, A. Togawa, K. Sogawa, T. Shida, F. Kimura, H. Shimizu, T. Tomonaga, F. Nomura, and M. Miyazaki. 2008. Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells. Oncogene 27: 2810–2822.

    Article  CAS  PubMed  Google Scholar 

  • Van Der Gun, B.T., L.J. Melchers, M.H. Ruiters, L.F. De Leij, P.M. Mclaughlin, and M.G. Rots. 2010. EpCAM in carcinogenesis: the good, the bad or the ugly. Carcinogenesis 31: 1913–1921.

    Article  PubMed  Google Scholar 

  • Vona, G., A. Sabile, M. Louha, V. Sitruk, S. Romana, K. Schutze, F. Capron, D. Franco, M. Pazzagli, M. Vekemans, B. Lacour, C. Brechot, and P. Paterlini-Brechot. 2000. Isolation by size of epithelial tumor cells—a new method for the immunomorphological and molecular characterization of circulating tumor cells. American Journal of Pathology 156: 57–63.

    Article  CAS  PubMed  Google Scholar 

  • Ward, D.G., N. Suggett, Y. Cheng, W. Wei, H. Johnson, L.J. Billingham, T. Ismail, M.J.O. Wakelam, P.J. Johnson, and A. Martin. 2006. Identification of serum biomarkers for colon cancer by proteomic analysis. British Journal of Cancer 94: 1898–1905.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Winter, M.J., I.D. Nagtegaal, J.H.J.M. Van Krieken, and S.V. Litvinov. 2003. The epithelial cell adhesion molecule (Ep-CAM) as a morphoregulatory molecule is a tool in surgical pathology. American Journal of Pathology 163: 2139–2148.

    Article  CAS  PubMed  Google Scholar 

  • Yu, M., S. Stott, M. Toner, S. Maheswaran, and D.A. Haber. 2011. Circulating tumor cells: approaches to isolation and characterization. Journal of Cell Biology 192: 373–382.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by KIST CTP Program (#2V03130) and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2008-0061891).

Author information

Authors and Affiliations

  1. Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA

    Kyobum Kim

  2. Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, South Korea

    Kwan Hyi Lee

  3. Department of Oral and Maxillofacial Surgery, Division of Dentistry Graduate School, Kyung-Hee University, Seoul, South Korea

    Jongmin Lee

  4. Department of BioNano Engineering, Hanyang University, ERICA Campus, Ansan, South Korea

    Jonghoon Choi

Authors
  1. Kyobum Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kwan Hyi Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jongmin Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jonghoon Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jonghoon Choi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, K., Lee, K.H., Lee, J. et al. Overview of current standpoints in profiling of circulating tumor cells. Arch. Pharm. Res. 37, 88–95 (2014). https://doi.org/10.1007/s12272-013-0285-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-013-0285-1

Keywords

Search

Navigation