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The Mammary Tumor Microenvironment

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Tumor Microenvironments in Organs

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1296))

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Abstract

A developing breast tumor is regulated by its tumor microenvironment (TME) which includes various immune cell subsets, fibroblasts, adipocytes, and endothelial and epithelial cells surrounded by an extracellular matrix (ECM). Breast tissue density is also a defining feature of breast cancer and plays an integral role in the exchange of biochemical cues between cells and the ECM. Cell signals from these interactions regulate tumor growth, metabolism, immunity, and invasion. The distinct organization of cells in the ECM generates structural patterns that are important in understanding disease development and progression. In this chapter, we discuss this complex interplay between the ECM and cells in the TME. Various models that mimic density are described to more fully understand the effect of ECM density on immunity, metabolism, tumorigenesis, and dormancy. Continued study of the interactions between cells and the ECM in the TME may provide needed biomarkers and therapeutic targets in breast cancer.

Support: R01CA216248, R01CA206458, and R01CA179556 to SMP, National Institutes of Health, Intramural Research Funds to CSC

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References

  1. ACS (2019) American Cancer Society. In: Breast cancer facts & figures 2019–2020. American Cancer Society, Inc., Atlanta, pp 1–44

    Google Scholar 

  2. Afik R, Zigmond E, Vugman M, Klepfish M, Shimshoni E, Pasmanik-Chor M, Shenoy A, Bassat E, Halpern Z, Geiger T, Sagi I, Varol C (2016) Tumor macrophages are pivotal constructors of tumor collagenous matrix. J Exp Med 213:2315–2331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Aguirre-Ghiso JA, Liu D, Mignatti A, Kovalski K, Ossowski L (2001) Urokinase receptor and fibronectin regulate the ERK(MAPK) to p38(MAPK) activity ratios that determine carcinoma cell proliferation or dormancy in vivo. Mol Biol Cell 12:863–879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Aguirre Ghiso JA, Kovalski K, Ossowski L (1999) Tumor dormancy induced by downregulation of urokinase receptor in human carcinoma involves integrin and MAPK signaling. J Cell Biol 147:89–104

    Article  CAS  PubMed  Google Scholar 

  5. Ali R, Wendt MK (2017) The paradoxical functions of EGFR during breast cancer progression. Signal Transduct Target Ther 2:16042

    Article  PubMed  PubMed Central  Google Scholar 

  6. An G, Wu F, Huang S, Feng L, Bai J, Gu S, Zhao X (2019) Effects of CCL5 on the biological behavior of breast cancer and the mechanisms of its interaction with tumorassociated macrophages. Oncol Rep 42:2499–2511

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Aponte-Lopez A, Fuentes-Panana EM, Cortes-Munoz D, Munoz-Cruz S (2018) Mast cell, the neglected member of the tumor microenvironment: role in breast cancer. J Immunol Res 2018:2584243

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Atabai K, Sheppard D, Werb Z (2007) Roles of the innate immune system in mammary gland remodeling during involution. J Mammary Gland Biol Neoplasia 12:37–45

    Article  PubMed  PubMed Central  Google Scholar 

  9. Bajgain P, Tawinwung S, D’elia L, Sukumaran S, Watanabe N, Hoyos V, Lulla P, Brenner MK, Leen AM, Vera JF (2018) CAR T cell therapy for breast cancer: harnessing the tumor milieu to drive T cell activation. J Immunother Cancer 6:34

    Article  PubMed  PubMed Central  Google Scholar 

  10. Barcus CE, O’leary KA, Brockman JL, Rugowski DE, Liu Y, Garcia N, Yu M, Keely PJ, Eliceiri KW, Schuler LA (2017) Elevated collagen-I augments tumor progressive signals, intravasation and metastasis of prolactin-induced estrogen receptor alpha positive mammary tumor cells. Breast Cancer Res 19:9

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Barkal AA, Brewer RE, Markovic M, Kowarsky M, Barkal SA, Zaro BW, Krishnan V, Hatakeyama J, Dorigo O, Barkal LJ, Weissman IL (2019) CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy. Nature 572:392–396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Barney LE, Hall CL, Schwartz AD, Parks AN, Sparages C, Galarza S, Platt MO, Mercurio AM, Peyton SR (2020) Tumor cell-organized fibronectin maintenance of a dormant breast cancer population. Sci Adv 6:eaaz4157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bayer SV, Grither WR, Brenot A, Hwang PY, Barcus CE, Ernst M, Pence P, Walter C, Pathak A, Longmore GD (2019) DDR2 controls breast tumor stiffness and metastasis by regulating integrin mediated mechanotransduction in CAFs. elife 8:e45508

    Article  PubMed  PubMed Central  Google Scholar 

  14. Beaty BT, Sharma VP, Bravo-Cordero JJ, Simpson MA, Eddy RJ, Koleske AJ, Condeelis J (2013) beta1 integrin regulates Arg to promote invadopodial maturation and matrix degradation. Mol Biol Cell 24(1661–75):S1–S11

    Google Scholar 

  15. Bershadsky A, Kozlov M, Geiger B (2006) Adhesion-mediated mechanosensitivity: a time to experiment, and a time to theorize. Curr Opin Cell Biol 18:472–481

    Article  CAS  PubMed  Google Scholar 

  16. Birbrair A, Zhang T, Wang ZM, Messi ML, Olson JD, Mintz A, Delbono O (2014) Type-2 pericytes participate in normal and tumoral angiogenesis. Am J Physiol Cell Physiol 307:C25–C38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bissell MJ, Radisky DC, Rizki A, Weaver VM, Petersen OW (2002) The organizing principle: microenvironmental influences in the normal and malignant breast. Differentiation 70:537–546

    Article  PubMed  PubMed Central  Google Scholar 

  18. Bott AJ, Peng IC, Fan Y, Faubert B, Zhao L, Li J, Neidler S, Sun Y, Jaber N, Krokowski D, Lu W, Pan JA, Powers S, Rabinowitz J, Hatzoglou M, Murphy DJ, Jones R, Wu S, Girnun G, Zong WX (2015) Oncogenic Myc induces expression of glutamine Synthetase through promoter demethylation. Cell Metab 22:1068–1077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Boyd NF, Guo H, Martin LJ, Sun L, Stone J, Fishell E, Jong RA, Hislop G, Chiarelli A, Minkin S, Yaffe MJ (2007) Mammographic density and the risk and detection of breast cancer. N Engl J Med 356:227–236

    Article  CAS  PubMed  Google Scholar 

  20. Boyd NF, Martin LJ, Bronskill M, Yaffe MJ, Duric N, Minkin S (2010) Breast tissue composition and susceptibility to breast cancer. J Natl Cancer Inst 102:1224–1237

    Article  PubMed  PubMed Central  Google Scholar 

  21. Bragado P, Estrada Y, Parikh F, Krause S, Capobianco C, Farina HG, Schewe DM, Aguirre-Ghiso JA (2013) TGF-beta2 dictates disseminated tumour cell fate in target organs through TGF-beta-RIII and p38alpha/beta signalling. Nat Cell Biol 15:1351–1361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Burrows N, Maxwell PH (2017) Hypoxia and B cells. Exp Cell Res 356:197–203

    Article  CAS  PubMed  Google Scholar 

  23. Cao MD, Lamichhane S, Lundgren S, Bofin A, Fjosne H, Giskeodegard GF, Bathen TF (2014) Metabolic characterization of triple negative breast cancer. BMC Cancer 14:941

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Carey SP, Martin KE, Reinhart-King CA (2017) Three-dimensional collagen matrix induces a mechanosensitive invasive epithelial phenotype. Sci Rep 7:42088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Catena R, Bhattacharya N, EL Rayes T, Wang S, Choi H, Gao D, Ryu S, Joshi N, Bielenberg D, Lee SB, Haukaas SA, Gravdal K, Halvorsen OJ, Akslen LA, Watnick RS, Mittal V (2013) Bone marrow-derived Gr1+ cells can generate a metastasis-resistant microenvironment via induced secretion of thrombospondin-1. Cancer Discov 3:578–589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Cha YJ, Jung WH, Koo JS (2017) Differential site-based expression of pentose phosphate pathway-related proteins among breast cancer metastases. Dis Markers 2017:7062517

    PubMed  PubMed Central  Google Scholar 

  27. Chang C, Goel HL, Gao H, Pursell B, Shultz LD, Greiner DL, Ingerpuu S, Patarroyo M, Cao S, Lim E, Mao J, Mckee KK, Yurchenco PD, Mercurio AM (2015) A laminin 511 matrix is regulated by TAZ and functions as the ligand for the alpha6Bbeta1 integrin to sustain breast cancer stem cells. Genes Dev 29:1–6

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Chew GL, Huo CW, Huang D, Hill P, Cawson J, Frazer H, Hopper JL, Haviv I, Henderson MA, Britt K, Thompson EW (2015) Increased COX-2 expression in epithelial and stromal cells of high mammographic density tissues and in a xenograft model of mammographic density. Breast Cancer Res Treat 153:89–99

    Article  CAS  PubMed  Google Scholar 

  29. Choquet D, Felsenfeld DP, Sheetz MP (1997) Extracellular matrix rigidity causes strengthening of integrin-cytoskeleton linkages. Cell 88:39–48

    Article  CAS  PubMed  Google Scholar 

  30. Chretien S, Zerdes I, Bergh J, Matikas A, Foukakis T (2019) Beyond PD-1/PD-L1 inhibition: what the future holds for breast cancer immunotherapy. Cancers (Basel) 11:628

    Article  CAS  Google Scholar 

  31. Christen S, Lorendeau D, Schmieder R, Broekaert D, Metzger K, Veys K, Elia I, Buescher JM, Orth MF, Davidson SM, Grunewald TG, De Bock K, Fendt SM (2016) Breast cancer-derived lung metastases show increased pyruvate carboxylase-dependent Anaplerosis. Cell Rep 17:837–848

    Article  CAS  PubMed  Google Scholar 

  32. Conklin MW, Eickhoff JC, Riching KM, Pehlke CA, Eliceiri KW, Provenzano PP, Friedl A, Keely PJ (2011) Aligned collagen is a prognostic signature for survival in human breast carcinoma. Am J Pathol 178:1221–1232

    Article  PubMed  PubMed Central  Google Scholar 

  33. Corsa CA, Brenot A, Grither WR, Van Hove S, Loza AJ, Zhang K, Ponik SM, Liu Y, Denardo DG, Eliceiri KW, Keely PJ, Longmore GD (2016) The action of Discoidin domain receptor 2 in basal tumor cells and stromal cancer-associated fibroblasts is critical for breast cancer metastasis. Cell Rep 15:2510–2523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Coughlin SS (2019) Epidemiology of breast cancer in women. Adv Exp Med Biol 1152:9–29

    Article  CAS  PubMed  Google Scholar 

  35. Curigliano G, Bagnardi V, Ghioni M, Louahed J, Brichard V, Lehmann FF, Marra A, Trapani D, Criscitiello C, Viale G (2020) Expression of tumor-associated antigens in breast cancer subtypes. Breast 49:202–209

    Article  PubMed  Google Scholar 

  36. Curran CS, Keely PJ (2013) Breast tumor and stromal cell responses to TGF-beta and hypoxia in matrix deposition. Matrix Biol 32:95–105

    Article  CAS  PubMed  Google Scholar 

  37. Czeisler C, Mikawa T (2013) Microtubules coordinate VEGFR2 signaling and sorting. PLoS One 8:e75833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. De Gramont A, Faivre S, Raymond E (2017) Novel TGF-beta inhibitors ready for prime time in onco-immunology. Onco Targets Ther 6:e1257453

    Google Scholar 

  39. Deberardinis RJ, Sayed N, Ditsworth D, Thompson CB (2008) Brick by brick: metabolism and tumor cell growth. Curr Opin Genet Dev 18:54–61

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Deligne C, Murdamoothoo D, Gammage AN, Gschwandtner M, Erne W, Loustau T, Marzeda AM, Carapito R, Paul N, Velazquez-Quesada I, Mazzier I, Sun Z, Orend G, Midwood KS (2020) Matrix-targeting immunotherapy controls tumor growth and spread by switching macrophage phenotype. Cancer Immunol Res 8:368–382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Delnero P, Hopkins BD, Cantley LC, Fischbach C (2018) Cancer metabolism gets physical. Sci Transl Med 10:eaaq1011

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Edechi CA, Ikeogu N, Uzonna JE, Myal Y (2019) Regulation of immunity in breast cancer. Cancers (Basel) 11:1080

    Article  CAS  Google Scholar 

  43. Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2:161–174

    Article  CAS  PubMed  Google Scholar 

  44. El Touny LH, Vieira A, Mendoza A, Khanna C, Hoenerhoff MJ, Green JE (2014) Combined SFK/MEK inhibition prevents metastatic outgrowth of dormant tumor cells. J Clin Invest 124:156–168

    Article  CAS  PubMed  Google Scholar 

  45. Elia I, Rossi M, Stegen S, Broekaert D, Doglioni G, Van Gorsel M, Boon R, Escalona-Noguero C, Torrekens S, Verfaillie C, Verbeken E, Carmeliet G, Fendt SM (2019) Breast cancer cells rely on environmental pyruvate to shape the metastatic niche. Nature 568:117–121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Esbona K, Inman D, Saha S, Jeffery J, Schedin P, Wilke L, Keely P (2016) COX-2 modulates mammary tumor progression in response to collagen density. Breast Cancer Res 18:35

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Esbona K, Yi Y, Saha S, Yu M, Van DOORN, R R, Conklin MW, Graham DS, Wisinski KB, Ponik SM, Eliceiri KW, Wilke LG, Keely PJ (2018) The presence of cyclooxygenase 2, tumor-associated macrophages, and collagen alignment as prognostic markers for invasive breast carcinoma patients. Am J Pathol 188:559–573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Esquivel-Velazquez M, Ostoa-Saloma P, Palacios-Arreola MI, Nava-Castro KE, Castro JI, Morales-Montor J (2015) The role of cytokines in breast cancer development and progression. J Interf Cytokine Res 35:1–16

    Article  CAS  Google Scholar 

  49. Ferruzzi J, Sun M, Gkousioudi A, Pilvar A, Roblyer D, Zhang Y, Zaman MH (2019) Compressive Remodeling alters fluid transport properties of collagen networks – implications for tumor growth. Sci Rep 9:17151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Fluegen G, Avivar-Valderas A, Wang Y, Padgen MR, Williams JK, Nobre AR, Calvo V, Cheung JF, Bravo-Cordero JJ, Entenberg D, Castracane J, Verkhusha V, Keely PJ, Condeelis J, Aguirre-Ghiso JA (2017) Phenotypic heterogeneity of disseminated tumour cells is preset by primary tumour hypoxic microenvironments. Nat Cell Biol 19:120–132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Fornetti J, Jindal S, Middleton KA, Borges VF, Schedin P (2014) Physiological COX-2 expression in breast epithelium associates with COX-2 levels in ductal carcinoma in situ and invasive breast cancer in young women. Am J Pathol 184:1219–1229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Fougner C, Bergholtz H, Kuiper R, Norum JH, Sorlie T (2019) Claudin-low-like mouse mammary tumors show distinct transcriptomic patterns uncoupled from genomic drivers. Breast Cancer Res 21:85

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Friedl P (2004) Prespecification and plasticity: shifting mechanisms of cell migration. Curr Opin Cell Biol 16:14–23

    Article  CAS  PubMed  Google Scholar 

  54. Friedl P, Wolf K (2003) Proteolytic and non-proteolytic migration of tumour cells and leucocytes. Biochem Soc Symp 70:277–285

    Article  CAS  Google Scholar 

  55. Friedl P, Wolf K (2008) Tube travel: the role of proteases in individual and collective cancer cell invasion. Cancer Res 68:7247–7249

    Article  CAS  PubMed  Google Scholar 

  56. Friedl P, Wolf K (2009) Proteolytic interstitial cell migration: a five-step process. Cancer Metastasis Rev 28:129–135

    Article  PubMed  Google Scholar 

  57. Friedl P, Wolf K (2010) Plasticity of cell migration: a multiscale tuning model. J Cell Biol 188:11–19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Garaud S, Buisseret L, Solinas C, Gu-Trantien C, de Wind A, Van Den Eynden G, Naveaux C, Lodewyckx JN, Boisson A, Duvillier H, Craciun L, Ameye L, Veys I, Paesmans M, Larsimont D, Piccart-Gebhart M, Willard-Gallo K (2019) Tumor infiltrating B-cells signal functional humoral immune responses in breast cancer. JCI Insight 13:5

    Google Scholar 

  59. Garcia-Mendoza MG, Inman DR, Ponik SM, Jeffery JJ, Sheerar DS, Van Doorn RR, Keely PJ (2016) Neutrophils drive accelerated tumor progression in the collagen-dense mammary tumor microenvironment. Breast Cancer Res 18:49

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Gastounioti A, Conant EF, Kontos D (2016) Beyond breast density: a review on the advancing role of parenchymal texture analysis in breast cancer risk assessment. Breast Cancer Res 18:91

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Ghajar CM, Peinado H, Mori H, Matei IR, Evason KJ, Brazier H, Almeida D, Koller A, Hajjar KA, Stainier DY, Chen EI, Lyden D, Bissell MJ (2013) The perivascular niche regulates breast tumour dormancy. Nat Cell Biol 15:807–817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Gilkes DM, Xiang L, Lee SJ, Chaturvedi P, Hubbi ME, Wirtz D, Semenza GL (2014) Hypoxia-inducible factors mediate coordinated RhoA-ROCK1 expression and signaling in breast cancer cells. Proc Natl Acad Sci U S A 111:E384–E393

    Article  CAS  PubMed  Google Scholar 

  63. Goetz JG, Minguet S, Navarro-Lerida I, Lazcano JJ, Samaniego R, Calvo E, Tello M, Osteso-Ibanez T, Pellinen T, Echarri A, Cerezo A, Klein-Szanto AJ, Garcia R, Keely PJ, Sanchez-Mateos P, Cukierman E, Del Pozo MA (2011) Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis. Cell 146:148–163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Goo CK, Lim HY, Ho QS, Too HP, Clement MV, Wong KP (2012) PTEN/Akt signaling controls mitochondrial respiratory capacity through 4E-BP1. PLoS One 7:e45806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Guo YP, Martin LJ, Hanna W, Banerjee D, Miller N, Fishell E, Khokha R, Boyd NF (2001) Growth factors and stromal matrix proteins associated with mammographic densities. Cancer Epidemiol Biomark Prev 10:243–248

    CAS  Google Scholar 

  66. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  CAS  PubMed  Google Scholar 

  67. Hansen KC, Kiemele L, Maller O, O’brien J, Shankar A, Fornetti J, Schedin P (2009) An in-solution ultrasonication-assisted digestion method for improved extracellular matrix proteome coverage. Mol Cell Proteomics 8:1648–1657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Harney AS, Arwert EN, Entenberg D, Wang Y, Guo P, Qian BZ, Oktay MH, Pollard JW, Jones JG, Condeelis JS (2015) Real-time imaging reveals local, transient vascular permeability, and tumor cell Intravasation stimulated by TIE2hi macrophage-derived VEGFA. Cancer Discov 5:932–943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Haston WS, Shields JM, Wilkinson PC (1982) Lymphocyte locomotion and attachment on two-dimensional surfaces and in three-dimensional matrices. J Cell Biol 92:747–752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Haukaas TH, Euceda LR, Giskeodegard GF, Lamichhane S, Krohn M, Jernstrom S, Aure MR, Lingjaerde OC, Schlichting E, Garred O, Due EU, Mills GB, Sahlberg KK, Borresen-Dale AL, Bathen TF, Oslo Breast Cancer, C (2016) Metabolic clusters of breast cancer in relation to gene- and protein expression subtypes. Cancer Metab 4:12

    Article  PubMed  PubMed Central  Google Scholar 

  71. Henley SJ, King JB, German RR, Richardson LC, Plescia M, Centers For Disease, C. & Prevention (2010) Surveillance of screening-detected cancers (colon and rectum, breast, and cervix) – United States, 2004–2006. MMWR Surveill Summ 59:1–25

    PubMed  Google Scholar 

  72. Hsu PP, Sabatini DM (2008) Cancer cell metabolism: Warburg and beyond. Cell 134:703–707

    Article  CAS  PubMed  Google Scholar 

  73. Hu W, Wang G, Huang D, Sui M, Xu Y (2019) Cancer immunotherapy based on natural killer cells: current Progress and new opportunities. Front Immunol 10:1205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Ilina O, Bakker GJ, Vasaturo A, Hofmann RM, Friedl P (2011) Two-photon laser-generated microtracks in 3D collagen lattices: principles of MMP-dependent and -independent collective cancer cell invasion. Phys Biol 8:015010

    Article  PubMed  CAS  Google Scholar 

  75. Insua-Rodriguez J, Oskarsson T (2016) The extracellular matrix in breast cancer. Adv Drug Deliv Rev 97:41–55

    Article  CAS  PubMed  Google Scholar 

  76. Ishihara J, Fukunaga K, Ishihara A, Larsson HM, Potin L, Hosseinchi P, Galliverti G, Swartz MA, Hubbell JA (2017a) Matrix-binding checkpoint immunotherapies enhance antitumor efficacy and reduce adverse events. Sci Transl Med 9:52

    Article  CAS  Google Scholar 

  77. Ishihara S, Inman DR, Li WJ, Ponik SM, Keely PJ (2017b) Mechano-signal transduction in mesenchymal stem cells induces prosaposin secretion to drive the proliferation of breast cancer cells. Cancer Res 77:6179–6189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Jahanban-Esfahlan R, Seidi K, Manjili MH, Jahanban-Esfahlan A, Javaheri T, Zare P (2019) Tumor cell dormancy: threat or opportunity in the fight against cancer. Cancers (Basel) 11:1207

    Article  CAS  Google Scholar 

  79. Jallow F, O’leary KA, Rugowski DE, Guerrero JF, Ponik SM, Schuler LA (2019) Dynamic interactions between the extracellular matrix and estrogen activity in progression of ER+ breast cancer. Oncogene 38:6913–6925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Jing W, Guo X, Wang G, Bi Y, Han L, Zhu Q, Qiu C, Tanaka M, Zhao Y (2020) Breast cancer cells promote CD169(+) macrophage-associated immunosuppression through JAK2-mediated PD-L1 upregulation on macrophages. Int Immunopharmacol 78:106012

    Article  CAS  PubMed  Google Scholar 

  81. Jung KH, Lee EJ, Park JW, Lee JH, Moon SH, Cho YS, Lee KH (2019) EGF receptor stimulation shifts breast cancer cell glucose metabolism toward glycolytic flux through PI3 kinase signaling. PLoS One 14:e0221294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Kalluri R, Zeisberg M (2006) Fibroblasts in cancer. Nat Rev Cancer 6:392–401

    Article  CAS  PubMed  Google Scholar 

  83. Keely PJ (2011) Mechanisms by which the extracellular matrix and integrin signaling act to regulate the switch between tumor suppression and tumor promotion. J Mammary Gland Biol Neoplasia 16:205–219

    Article  PubMed  Google Scholar 

  84. Kessenbrock K, Plaks V, Werb Z (2010) Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141:52–67

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Khamis ZI, Sahab ZJ, Sang QX (2012) Active roles of tumor stroma in breast cancer metastasis. Int J Breast Cancer 2012:574025

    Article  PubMed  PubMed Central  Google Scholar 

  86. Kim HM, Jung WH, Koo JS (2014) Site-specific metabolic phenotypes in metastatic breast cancer. J Transl Med 12:354

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Kozlova N, Wottawa M, Katschinski DM, Kristiansen G, Kietzmann T (2017) Hypoxia-inducible factor prolyl hydroxylase 2 (PHD2) is a direct regulator of epidermal growth factor receptor (EGFR) signaling in breast cancer. Oncotarget 8:9885–9898

    Article  PubMed  Google Scholar 

  88. Kuczek DE, Larsen AMH, Thorseth ML, Carretta M, Kalvisa A, Siersbaek MS, Simoes AMC, Roslind A, Engelholm LH, Noessner E, Donia M, Svane IM, Straten PT, Grontved L, Madsen DH (2019) Collagen density regulates the activity of tumor-infiltrating T cells. J Immunother Cancer 7:68

    Article  PubMed  PubMed Central  Google Scholar 

  89. Kurelac I, Umesh Ganesh N, Iorio M, Porcelli AM, Gasparre G (2020) The multifaceted effects of metformin on tumor microenvironment. Semin Cell Dev Biol 98:90–97

    Article  CAS  PubMed  Google Scholar 

  90. Kuznetsova M, Lopatnikova J, Shevchenko J, Silkov A, Maksyutov A, Sennikov S (2019) Cytotoxic activity and memory T cell subset distribution of in vitro-stimulated CD8(+) T cells specific for HER2/neu epitopes. Front Immunol 10:1017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Lee K, Chen QK, Lui C, Cichon MA, Radisky DC, Nelson CM (2012) Matrix compliance regulates Rac1b localization, NADPH oxidase assembly, and epithelial-mesenchymal transition. Mol Biol Cell 23:4097–4108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Levental KR, Yu H, Kass L, Lakins JN, Egeblad M, Erler JT, Fong SF, Csiszar K, Giaccia A, Weninger W, Yamauchi M, Gasser DL, Weaver VM (2009) Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 139:891–906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Lin EY, Nguyen AV, Russell RG, Pollard JW (2001) Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med 193:727–740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Liu Q, Zhang H, Jiang X, Qian C, Liu Z, Luo D (2017) Factors involved in cancer metastasis: a better understanding to “seed and soil” hypothesis. Mol Cancer 16:176

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Liu X, Wu H, Byrne M, Jeffrey J, Krane S, Jaenisch R (1995) A targeted mutation at the known collagenase cleavage site in mouse type I collagen impairs tissue remodeling. J Cell Biol 130:227–237

    Article  CAS  PubMed  Google Scholar 

  96. Mah EJ, Lefebvre A, Mcgahey GE, Yee AF, Digman MA (2018) Collagen density modulates triple-negative breast cancer cell metabolism through adhesion-mediated contractility. Sci Rep 8:17094

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Malladi S, Macalinao DG, Jin X, He L, Basnet H, Zou Y, De Stanchina E, Massague J (2016) Metastatic latency and immune evasion through autocrine inhibition of WNT. Cell 165:45–60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Mardakheh FK, Paul A, Kumper S, Sadok A, Paterson H, Mccarthy A, Yuan Y, Marshall CJ (2015) Global analysis of mRNA, translation, and protein localization: local translation is a key regulator of cell protrusions. Dev Cell 35:344–357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Marlow R, Honeth G, Lombardi S, Cariati M, Hessey S, Pipili A, Mariotti V, Buchupalli B, Foster K, Bonnet D, Grigoriadis A, Rameshwar P, Purushotham A, Tutt A, Dontu G (2013) A novel model of dormancy for bone metastatic breast cancer cells. Cancer Res 73:6886–6899

    Article  CAS  PubMed  Google Scholar 

  100. Mecham RP (2012) Overview of extracellular matrix. Curr Protoc Cell Biol, Chapter 10, Unit 10 1

    Google Scholar 

  101. Meissner M, Pinter A, Michailidou D, Hrgovic I, Kaprolat N, Stein M, Holtmeier W, Kaufmann R, Gille J (2008) Microtubule-targeted drugs inhibit VEGF receptor-2 expression by both transcriptional and post-transcriptional mechanisms. J Invest Dermatol 128:2084–2091

    Article  CAS  PubMed  Google Scholar 

  102. Mierke CT, Bretz N, Altevogt P (2011) Contractile forces contribute to increased glycosylphosphatidylinositol-anchored receptor CD24-facilitated cancer cell invasion. J Biol Chem 286:34858–34871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Miron-Mendoza M, Seemann J, Grinnell F (2008) Collagen fibril flow and tissue translocation coupled to fibroblast migration in 3D collagen matrices. Mol Biol Cell 19:2051–2058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Morris BA, Burkel B, Ponik SM, Fan J, Condeelis JS, Aguirre-Ghiso JA, Castracane J, Denu JM, Keely PJ (2016) Collagen matrix density drives the metabolic shift in breast cancer cells. EBioMedicine 13:146–156

    Article  PubMed  PubMed Central  Google Scholar 

  105. Mouchemore KA, Anderson RL, Hamilton JA (2018) Neutrophils, G-CSF and their contribution to breast cancer metastasis. FEBS J 285:665–679

    Article  CAS  PubMed  Google Scholar 

  106. Muir A, Danai LV, Vander Heiden MG (2018) Microenvironmental regulation of cancer cell metabolism: implications for experimental design and translational studies. Dis Model Mech 11:dmm035758

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  107. Naba A, Clauser KR, Hoersch S, Liu H, Carr SA, Hynes RO (2012) The matrisome: in silico definition and in vivo characterization by proteomics of normal and tumor extracellular matrices. Mol Cell Proteomics 11:M111 014647

    Article  PubMed  CAS  Google Scholar 

  108. Nissen NI, Karsdal M, Willumsen N (2019) Collagens and cancer associated fibroblasts in the reactive stroma and its relation to cancer biology. J Exp Clin Cancer Res 38:115

    Article  PubMed  PubMed Central  Google Scholar 

  109. O’brien JH, Vanderlinden LA, Schedin PJ, Hansen KC (2012) Rat mammary extracellular matrix composition and response to ibuprofen treatment during postpartum involution by differential GeLC-MS/MS analysis. J Proteome Res 11:4894–4905

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. Onesti CE, Boemer F, Josse C, Leduc S, Bours V, Jerusalem G (2019) Tryptophan catabolism increases in breast cancer patients compared to healthy controls without affecting the cancer outcome or response to chemotherapy. J Transl Med 17:239

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  111. Paez D, Labonte MJ, Bohanes P, Zhang W, Benhanim L, Ning Y, Wakatsuki T, Loupakis F, Lenz HJ (2012) Cancer dormancy: a model of early dissemination and late cancer recurrence. Clin Cancer Res 18:645–653

    Article  PubMed  Google Scholar 

  112. Paget S (1989) The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev 8:98–101

    CAS  PubMed  Google Scholar 

  113. Paiva AE, Lousado L, Guerra DAP, Azevedo PO, Sena IFG, Andreotti JP, Santos GSP, Goncalves R, Mintz A, Birbrair A (2018) Pericytes in the Premetastatic niche. Cancer Res 78:2779–2786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Pakshir P, Alizadehgiashi M, Wong B, Coelho NM, Chen X, Gong Z, Shenoy VB, Mcculloch CA, Hinz B (2019) Dynamic fibroblast contractions attract remote macrophages in fibrillar collagen matrix. Nat Commun 10:1850

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Pan H, Gray R, Braybrooke J, Davies C, Taylor C, Mcgale P, Peto R, Pritchard KI, Bergh J, Dowsett M, Hayes DF, EBCTCG (2017) 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med 377:1836–1846

    Article  PubMed  PubMed Central  Google Scholar 

  116. Pang MF, Siedlik MJ, Han S, Stallings-Mann M, Radisky DC, Nelson CM (2016) Tissue stiffness and hypoxia modulate the integrin-linked kinase ILK to control breast cancer stem-like cells. Cancer Res 76:5277–5287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Paszek MJ, Zahir N, Johnson KR, Lakins JN, Rozenberg GI, Gefen A, Reinhart-King CA, Margulies SS, Dembo M, Boettiger D, Hammer DA, Weaver VM (2005) Tensional homeostasis and the malignant phenotype. Cancer Cell 8:241–254

    Article  CAS  PubMed  Google Scholar 

  118. Pike MC, Pearce CL (2013) Mammographic density, MRI background parenchymal enhancement and breast cancer risk. Ann Oncol 24(Suppl 8):viii37–viii41

    Article  PubMed  PubMed Central  Google Scholar 

  119. Ponik SM, Trier SM, Wozniak MA, Eliceiri KW, Keely PJ (2013) RhoA is down-regulated at cell-cell contacts via p190RhoGAP-B in response to tensional homeostasis. Mol Biol Cell 24(1688–99):S1–S3

    Google Scholar 

  120. Provenzano PP, Eliceiri KW, Campbell JM, Inman DR, White JG, Keely PJ (2006) Collagen reorganization at the tumor-stromal interface facilitates local invasion. BMC Med 4:38

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  121. Provenzano PP, Inman DR, Eliceiri KW, Keely PJ (2009) Matrix density-induced mechanoregulation of breast cell phenotype, signaling and gene expression through a FAK-ERK linkage. Oncogene 28:4326–4343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Provenzano PP, Inman DR, Eliceiri KW, Knittel JG, Yan L, Rueden CT, White JG, Keely PJ (2008) Collagen density promotes mammary tumor initiation and progression. BMC Med 6:11

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Ray A, Slama ZM, Morford RK, Madden SA, Provenzano PP (2017) Enhanced directional migration of cancer stem cells in 3D aligned collagen matrices. Biophys J 112:1023–1036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Reed JR, Schwertfeger KL (2010) Immune cell location and function during post-natal mammary gland development. J Mammary Gland Biol Neoplasia 15:329–339

    Article  PubMed  PubMed Central  Google Scholar 

  125. Riabov V, Gudima A, Wang N, Mickley A, Orekhov A, Kzhyshkowska J (2014) Role of tumor associated macrophages in tumor angiogenesis and lymphangiogenesis. Front Physiol 5:75

    Article  PubMed  PubMed Central  Google Scholar 

  126. Ribeiro AL, Okamoto OK (2015) Combined effects of pericytes in the tumor microenvironment. Stem Cells Int 2015:868475

    Article  PubMed  PubMed Central  Google Scholar 

  127. Riching KM, Cox BL, Salick MR, Pehlke C, Riching AS, Ponik SM, Bass BR, Crone WC, Jiang Y, Weaver AM, Eliceiri KW, Keely PJ (2014) 3D collagen alignment limits protrusions to enhance breast cancer cell persistence. Biophys J 107:2546–2558

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Riching KM, Keely PJ (2015) Rho family GTPases: making it to the third dimension. Int J Biochem Cell Biol 59:111–115

    Article  CAS  PubMed  Google Scholar 

  129. Richman J, Dowsett M (2019) Beyond 5 years: enduring risk of recurrence in oestrogen receptor-positive breast cancer. Nat Rev Clin Oncol 16:296–311

    Article  CAS  PubMed  Google Scholar 

  130. Robinson BD, Sica GL, Liu YF, Rohan TE, Gertler FB, Condeelis JS, Jones JG (2009) Tumor microenvironment of metastasis in human breast carcinoma: a potential prognostic marker linked to hematogenous dissemination. Clin Cancer Res 15:2433–2441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Rothenberg KE, Scott DW, Christoforou N, Hoffman BD (2018) Vinculin force-sensitive dynamics at focal adhesions enable effective directed cell migration. Biophys J 114:1680–1694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Sabeh F, Shimizu-Hirota R, Weiss SJ (2009) Protease-dependent versus -independent cancer cell invasion programs: three-dimensional amoeboid movement revisited. J Cell Biol 185:11–19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Saleh R, Toor SM, Khalaf S, Elkord E (2019) Breast cancer cells and PD-1/PD-L1 blockade upregulate the expression of PD-1, CTLA-4, TIM-3 and LAG-3 immune checkpoints in CD4(+) T cells. Vaccines (Basel) 7:149

    Article  CAS  Google Scholar 

  134. Santoro A, Vlachou T, Luzi L, Melloni G, Mazzarella L, D’elia E, Aobuli X, Pasi CE, Reavie L, Bonetti P, Punzi S, Casoli L, Sabo A, Moroni MC, Dellino GI, Amati B, Nicassio F, Lanfrancone L, Pelicci PG (2019) p53 loss in breast cancer leads to Myc activation, increased cell plasticity, and expression of a mitotic signature with prognostic value. Cell Rep 26:624–638. e8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Saxena M, Liu S, Yang B, Hajal C, Changede R, Hu J, Wolfenson H, Hone J, Sheetz MP (2017) EGFR and HER2 activate rigidity sensing only on rigid matrices. Nat Mater 16:775–781

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Schofield AV, Steel R, Bernard O (2012) Rho-associated coiled-coil kinase (ROCK) protein controls microtubule dynamics in a novel signaling pathway that regulates cell migration. J Biol Chem 287:43620–43629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Schreiber RD, Old LJ, Smyth MJ (2011) Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science 331:1565–1570

    Article  CAS  PubMed  Google Scholar 

  138. SEER (2019) Surveillance, Epidemiology, and End Results (SEER) Program Stat Database: Incidence – SEER 9 Regs Research Data, Nov 2018 Sub (1975–2016)

    Google Scholar 

  139. Segovia-Mendoza M, Morales-Montor J (2019) Immune tumor microenvironment in breast cancer and the participation of Estrogen and its receptors in Cancer physiopathology. Front Immunol 10:348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Seow DYB, Yeong JPS, Lim JX, Chia N, Lim JCT, Ong CCH, Tan PH, Iqbal J (2020) Tertiary lymphoid structures and associated plasma cells play an important role in the biology of triple-negative breast cancers. Breast Cancer Res Treat 180:369–377

    Article  CAS  PubMed  Google Scholar 

  141. Shao X, Taha IN, Clauser KR, Gao YT, Naba A (2020) MatrisomeDB: the ECM-protein knowledge database. Nucleic Acids Res 48:D1136–D1144

    Article  CAS  PubMed  Google Scholar 

  142. Shen L, O’shea JM, Kaadige MR, Cunha S, Wilde BR, Cohen AL, Welm AL, Ayer DE (2015) Metabolic reprogramming in triple-negative breast cancer through Myc suppression of TXNIP. Proc Natl Acad Sci U S A 112:5425–5430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Shevchenko JA, Khristin AA, Kurilin VV, Kuznetsova MS, Blinova DD, Starostina NM, Sidorov SV, Sennikov SV (2020) Autologous dendritic cells and activated cytotoxic Tcells as combination therapy for breast cancer. Oncol Rep 43:671–680

    CAS  PubMed  Google Scholar 

  144. Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin 69:7–34

    Article  PubMed  Google Scholar 

  145. Sosa MS, Parikh F, Maia AG, Estrada Y, Bosch A, Bragado P, Ekpin E, George A, Zheng Y, Lam HM, Morrissey C, Chung CY, Farias EF, Bernstein E, Aguirre-Ghiso JA (2015) NR2F1 controls tumour cell dormancy via SOX9- and RARbeta-driven quiescence programmes. Nat Commun 6:6170

    Article  CAS  PubMed  Google Scholar 

  146. Summers C, Rankin SM, Condliffe AM, Singh N, Peters AM, Chilvers ER (2010) Neutrophil kinetics in health and disease. Trends Immunol 31:318–324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Sun Z, Schwenzer A, Rupp T, Murdamoothoo D, Vegliante R, Lefebvre O, Klein A, Hussenet T, Orend G (2018) Tenascin-C promotes tumor cell migration and metastasis through integrin alpha9beta1-mediated YAP inhibition. Cancer Res 78:950–961

    Article  CAS  PubMed  Google Scholar 

  148. Sung BH, Weaver AM (2017) Exosome secretion promotes chemotaxis of cancer cells. Cell Adhes Migr 11:187–195

    Article  CAS  Google Scholar 

  149. Sung KE, Yang N, Pehlke C, Keely PJ, Eliceiri KW, Friedl A, Beebe DJ (2011) Transition to invasion in breast cancer: a microfluidic in vitro model enables examination of spatial and temporal effects. Integr Biol (Camb) 3:439–450

    Article  CAS  Google Scholar 

  150. Tayyari F, Gowda GAN, Olopade OF, Berg R, Yang HH, Lee MP, Ngwa WF, Mittal SK, Raftery D, Mohammed SI (2018) Metabolic profiles of triple-negative and luminal a breast cancer subtypes in African-American identify key metabolic differences. Oncotarget 9:11677–11690

    Article  PubMed  PubMed Central  Google Scholar 

  151. Tomko LA, Hill RC, Barrett A, Szulczewski JM, Conklin MW, Eliceiri KW, Keely PJ, Hansen KC, Ponik SM (2018) Targeted matrisome analysis identifies thrombospondin-2 and tenascin-C in aligned collagen stroma from invasive breast carcinoma. Sci Rep 8:12941

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  152. Toor SM, Syed Khaja AS, El Salhat H, Faour I, Kanbar J, Quadri AA, Albashir M, Elkord E (2017) Myeloid cells in circulation and tumor microenvironment of breast cancer patients. Cancer Immunol Immunother 66:753–764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Tseng CW, Kuo WH, Chan SH, Chan HL, Chang KJ, Wang LH (2018) Transketolase regulates the metabolic switch to control breast cancer cell metastasis via the alpha-Ketoglutarate Signaling pathway. Cancer Res 78:2799–2812

    Article  CAS  PubMed  Google Scholar 

  154. Ueno T, Toi M, Saji H, Muta M, Bando H, Kuroi K, Koike M, Inadera H, Matsushima K (2000) Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer. Clin Cancer Res 6:3282–3289

    CAS  PubMed  Google Scholar 

  155. Varricchi G, Galdiero MR, Loffredo S, Lucarini V, Marone G, Mattei F, Marone G, Schiavoni G (2018) Eosinophils: the unsung heroes in cancer? Onco Targets Ther 7:e1393134

    Google Scholar 

  156. Velez DO, Ranamukhaarachchi SK, Kumar A, Modi RN, Lim EW, Engler AJ, Metallo CM, Fraley SI (2019) 3D collagen architecture regulates cell adhesion through degradability, thereby controlling metabolic and oxidative stress. Integr Biol (Camb) 11:221–234

    Article  PubMed Central  Google Scholar 

  157. Wang C, Mayer JA, Mazumdar A, Fertuck K, Kim H, Brown M, Brown PH (2011) Estrogen induces c-myc gene expression via an upstream enhancer activated by the estrogen receptor and the AP-1 transcription factor. Mol Endocrinol 25:1527–1538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Wang JB, Erickson JW, Fuji R, Ramachandran S, Gao P, Dinavahi R, Wilson KF, Ambrosio AL, Dias SM, Dang CV, Cerione RA (2010) Targeting mitochondrial glutaminase activity inhibits oncogenic transformation. Cancer Cell 18:207–219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Wang T, Hamilla S, Cam M, Aranda-Espinoza H, Mili S (2017) Extracellular matrix stiffness and cell contractility control RNA localization to promote cell migration. Nat Commun 8:896

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Wennerberg E, Spada S, Rudqvist NP, Lhuillier C, Gruber S, Chen Q, Zhang F, Zhou XK, Gross SS, Formenti SC, Demaria S (2020) CD73 blockade promotes dendritic cell infiltration of irradiated tumors and tumor rejection. Cancer Immunol Res 8:465–478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Wolf K, Mazo I, Leung H, Engelke K, Von Andrian UH, Deryugina EI, Strongin AY, Brocker EB, Friedl P (2003) Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis. J Cell Biol 160:267–277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Wolfe JN (1976) Breast patterns as an index of risk for developing breast cancer. AJR Am J Roentgenol 126:1130–1137

    Article  CAS  PubMed  Google Scholar 

  163. Wozniak MA, Desai R, Solski PA, Der CJ, Keely PJ (2003) ROCK-generated contractility regulates breast epithelial cell differentiation in response to the physical properties of a three-dimensional collagen matrix. J Cell Biol 163:583–595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Wu L, Saxena S, Singh RK (2020) Neutrophils in the tumor microenvironment. Adv Exp Med Biol 1224:1–20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Wyckoff J, Wang W, Lin EY, Wang Y, Pixley F, Stanley ER, Graf T, Pollard JW, Segall J, Condeelis J (2004) A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res 64:7022–7029

    Article  CAS  PubMed  Google Scholar 

  166. Yang N, Friedl A (2016) Syndecan-1-induced ECM Fiber alignment requires integrin alphavbeta3 and Syndecan-1 Ectodomain and Heparan Sulfate chains. PLoS One 11:e0150132

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  167. Yang N, Mosher R, Seo S, Beebe D, Friedl A (2011) Syndecan-1 in breast cancer stroma fibroblasts regulates extracellular matrix fiber organization and carcinoma cell motility. Am J Pathol 178:325–335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Yuneva MO, Fan TW, Allen TD, Higashi RM, Ferraris DV, Tsukamoto T, Mates JM, Alonso FJ, Wang C, Seo Y, Chen X, Bishop JM (2012) The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type. Cell Metab 15:157–170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Zanotelli MR, Goldblatt ZE, Miller JP, Bordeleau F, Li J, Vanderburgh JA, Lampi MC, King MR, Reinhart-King CA (2018) Regulation of ATP utilization during metastatic cell migration by collagen architecture. Mol Biol Cell 29:1–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Zhang H, Fredericks T, Xiong G, Qi Y, Rychahou PG, Li JD, Pihlajaniemi T, Xu W, Xu R (2018) Membrane associated collagen XIII promotes cancer metastasis and enhances anoikis resistance. Breast Cancer Res 20:116

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Critical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, USA

    Colleen S. Curran

  2. Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI, USA

    Suzanne M. Ponik

  3. University of Wisconsin Carbone Cancer Center, Madison, WI, USA

    Suzanne M. Ponik

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  1. Colleen S. Curran
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Correspondence to Suzanne M. Ponik .

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  1. Department of Radiology, Columbia University Medical Center, New York, NY, USA, Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Alexander Birbrair

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Curran, C.S., Ponik, S.M. (2020). The Mammary Tumor Microenvironment. In: Birbrair, A. (eds) Tumor Microenvironments in Organs. Advances in Experimental Medicine and Biology, vol 1296. Springer, Cham. https://doi.org/10.1007/978-3-030-59038-3_10

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