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Role of Stroma in Disease Progression

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Experimental and Clinical Metastasis

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Abstract

In the past, most research into cancer initiation and development, as well as into the progression from local to systemic disease, has focused on the tumor tissue per se. However, it is becoming increasingly evident that the configuration of the local microenvironment, and the nature of dynamic interactions occurring between cellular and structural elements of the stroma (generally defined as those tissue components distal to the basement membrane in normal tissue) and the tumor, can play significant roles. An understanding of these interactions will thus facilitate the development of strategies to manipulate the microenvironment, which are likely to represent the next important set of additions to the therapeutic armamentarium. Here, we describe the processes occurring in tumor stroma, using breast cancer as a model system.

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References

  • Allinen M et al (2004) Molecular characterization of the tumor microenvironment in breast cancer. Cancer Cell 6:17–32

    Article  PubMed  CAS  Google Scholar 

  • Andarawewa KL et al (2005) Stromelysin-3 is a potent negative regulator of adipogenesis participating to cancer cell-adipocyte interaction/crosstalk at the tumor invasive front. Cancer Res 65:10862–10871

    Article  PubMed  CAS  Google Scholar 

  • Anderson CF, Mosser DM (2002) A novel phenotype for an activated macrophage: the type 2 activated macrophage. J Leukoc Biol 72:101–106

    PubMed  CAS  Google Scholar 

  • Arenberg DA et al (2000) Macrophage infiltration in human non-small-cell lung cancer: the role of CC chemokines. Cancer Immunol Immunother 49:63–70

    Article  PubMed  CAS  Google Scholar 

  • Balkwill F (2004) Cancer and the chemokine network. Nat Rev Cancer 4:540–550

    Article  PubMed  CAS  Google Scholar 

  • Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357:539–545

    Article  PubMed  CAS  Google Scholar 

  • Balkwill F, Charles KA, Mantovani A (2005) Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 7:211–217

    Article  PubMed  CAS  Google Scholar 

  • Bates GJ et al (2006) Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol 24:5373–5380

    Article  PubMed  Google Scholar 

  • Bergamaschi A et al (2008) Extracellular matrix signature identifies breast cancer subgroups with different clinical outcome. J Pathol 214:357–367

    Article  PubMed  CAS  Google Scholar 

  • Bingle L, Brown NJ, Lewis CE (2002) The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol 196:254–265

    Article  PubMed  CAS  Google Scholar 

  • Boersma BJ et al (2008) A stromal gene signature associated with inflammatory breast cancer. Int J Cancer 122:1324–1332

    Article  PubMed  CAS  Google Scholar 

  • Bohling SD, Allison KH (2008) Immunosuppressive regulatory T cells are associated with aggressive breast cancer phenotypes: a potential therapeutic target. Mod Pathol 21:1527–1532

    Article  PubMed  CAS  Google Scholar 

  • Bottazzi B et al (1983) Regulation of the macrophage content of neoplasms by chemoattractants. Science 220:210–212

    Article  PubMed  CAS  Google Scholar 

  • Boyd NF et al (2002) Heritability of mammographic density, a risk factor for breast cancer. N Engl J Med 347:886–894

    Article  PubMed  Google Scholar 

  • Brown DM, Ruoslahti E (2004) Metadherin, a cell surface protein in breast tumors that mediates lung metastasis. Cancer Cell 5:365–374

    Article  PubMed  CAS  Google Scholar 

  • Buess M et al (2007) Characterization of heterotypic interaction effects in vitro to deconvolute global gene expression profiles in cancer. Genome Biol 8:R191

    Article  PubMed  CAS  Google Scholar 

  • Casey T et al (2009) Molecular signatures suggest a major role for stromal cells in development of invasive breast cancer. Breast Cancer Res Treat 114:47–62

    Article  PubMed  CAS  Google Scholar 

  • Castello-Cros R, Khan DR, Simons J, Valianou M, Cukierman E (2009) Staged stromal extracellular 3D matrices differentially regulate breast cancer cell responses through PI3K and beta1-integrins. BMC Cancer 9:94

    Article  PubMed  CAS  Google Scholar 

  • Catalano S et al (2003) Leptin enhances, via AP-1, expression of aromatase in the MCF-7 cell line. J Biol Chem 278:28668–28676

    Article  PubMed  CAS  Google Scholar 

  • Catalano S et al (2004) Leptin induces, via ERK1/ERK2 signal, functional activation of estrogen receptor alpha in MCF-7 cells. J Biol Chem 279:19908–19915

    Article  PubMed  CAS  Google Scholar 

  • Catalano S et al (2009) Evidence that leptin through STAT and CREB signaling enhances cyclin D1 expression and promotes human endometrial cancer proliferation. J Cell Physiol 218:490–500

    Article  PubMed  CAS  Google Scholar 

  • Chang HY et al (2004) Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds. PLoS Biol 2:E7

    Article  PubMed  CAS  Google Scholar 

  • Chang HY et al (2005) Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival. Proc Natl Acad Sci U S A 102:3738–3743

    Article  PubMed  CAS  Google Scholar 

  • Cirillo D, Rachiglio AM, la Montagna R, Giordano A, Normanno N (2008) Leptin signaling in breast cancer: an overview. J Cell Biochem 105:956–964

    Article  PubMed  CAS  Google Scholar 

  • Clynes RA, Towers TL, Presta LG, Ravetch JV (2000) Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Nat Med 6:443–446

    Article  PubMed  CAS  Google Scholar 

  • Coleman RE (2009) Adjuvant bisphosphonates in breast cancer: are we witnessing the emergence of a new therapeutic strategy? Eur J Cancer 45:1909–1915

    Article  PubMed  CAS  Google Scholar 

  • Condeelis J, Pollard JW (2006) Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 124:263–266

    Article  PubMed  CAS  Google Scholar 

  • Condeelis J, Segall JE (2003) Intravital imaging of cell movement in tumours. Nat Rev Cancer 3:921–930

    Article  PubMed  CAS  Google Scholar 

  • Cooley S, Burns LJ, Repka T, Miller JS (1999) Natural killer cell cytotoxicity of breast cancer targets is enhanced by two distinct mechanisms of antibody-dependent cellular cytotoxicity against LFA-3 and HER2/neu. Exp Hematol 27:1533–1541

    Article  PubMed  CAS  Google Scholar 

  • Corsini C et al (2003) Stroma cells: a novel target of herceptin activity. Clin Cancer Res 9:1820–1825

    PubMed  CAS  Google Scholar 

  • Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867

    Article  PubMed  CAS  Google Scholar 

  • Dieudonne MN et al (2006) Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells. Biochem Biophys Res Commun 345:271–279

    Article  PubMed  CAS  Google Scholar 

  • Dos Santos E et al (2008) Adiponectin mediates an antiproliferative response in human MDA-MB 231 breast cancer cells. Oncol Rep 20:971–977

    PubMed  Google Scholar 

  • Elliott BE, Tam SP, Dexter D, Chen ZQ (1992) Capacity of adipose tissue to promote growth and metastasis of a murine mammary carcinoma: effect of estrogen and progesterone. Int J Cancer 51:416–424

    Article  PubMed  CAS  Google Scholar 

  • Eneman JD, Wood ME, Muss HB (2004) Selecting adjuvant endocrine therapy for breast cancer. Oncology (Williston Park) 18:1733–1744 (discussion 1744–5, 1748, 1751–4)

    Google Scholar 

  • Farmer P et al (2009) A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer. Nat Med 15:68–74

    Article  PubMed  CAS  Google Scholar 

  • Finak G et al (2006) Gene expression signatures of morphologically normal breast tissue identify basal-like tumors. Breast Cancer Res 8:R58

    Article  PubMed  CAS  Google Scholar 

  • Finak G et al (2008) Stromal gene expression predicts clinical outcome in breast cancer. Nat Med 14:518–527

    Article  PubMed  CAS  Google Scholar 

  • Fleming JM et al (2008) Interlobular and intralobular mammary stroma: genotype may not reflect phenotype. BMC Cell Biol 9:46

    Article  PubMed  CAS  Google Scholar 

  • Fukino K et al (2004) Combined total genome loss of heterozygosity scan of breast cancer stroma and epithelium reveals multiplicity of stromal targets. Cancer Res 64:7231–7236

    Article  PubMed  CAS  Google Scholar 

  • Fukino K, Shen L, Patocs A, Mutter GL, Eng C (2007) Genomic instability within tumor stroma and clinicopathological characteristics of sporadic primary invasive breast carcinoma. JAMA 297:2103–2111

    Article  PubMed  CAS  Google Scholar 

  • Garcia S et al (2007a) Overexpression of c-Met and of the transducers PI3K, FAK and JAK in breast carcinomas correlates with shorter survival and neoangiogenesis. Int J Oncol 31:49–58

    Google Scholar 

  • Garcia S et al (2007b) Poor prognosis in breast carcinomas correlates with increased expression of targetable CD146 and c-Met and with proteomic basal-like phenotype. Hum Pathol 38:830–841

    Article  CAS  Google Scholar 

  • Gennari R et al (2004) Pilot study of the mechanism of action of preoperative trastuzumab in patients with primary operable breast tumors overexpressing HER2. Clin Cancer Res 10:5650–5655

    Article  PubMed  CAS  Google Scholar 

  • Giannopoulou I et al (2007) The prognostic value of the topographic distribution of uPAR expression in invasive breast carcinomas. Cancer Lett 246:262–267

    Article  PubMed  CAS  Google Scholar 

  • Goswami S et al (2005) Macrophages promote the invasion of breast carcinoma cells via a colony-stimulating factor-1/epidermal growth factor paracrine loop. Cancer Res 65:5278–5283

    Article  PubMed  CAS  Google Scholar 

  • Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140:883–899

    Article  PubMed  CAS  Google Scholar 

  • Gudjonsson T et al (2002) Normal and tumor-derived myoepithelial cells differ in their ability to interact with luminal breast epithelial cells for polarity and basement membrane deposition. J Cell Sci 115:39–50

    PubMed  CAS  Google Scholar 

  • Halsted KC et al (2008) Collagen alpha1(XI) in normal and malignant breast tissue. Mod Pathol 21:1246–1254

    Article  PubMed  CAS  Google Scholar 

  • Hattar R et al (2009) Tamoxifen induces pleiotrophic changes in mammary stroma resulting in extracellular matrix that suppresses transformed phenotypes. Breast Cancer Res 11:R5

    Article  PubMed  CAS  Google Scholar 

  • Hawsawi NM et al (2008) Breast carcinoma-associated fibroblasts and their counterparts display neoplastic-specific changes. Cancer Res 68:2717–2725

    Article  PubMed  CAS  Google Scholar 

  • Hill R, Song Y, Cardiff RD, Van Dyke T (2005) Selective evolution of stromal mesenchyme with p53 loss in response to epithelial tumorigenesis. Cell 123:1001–1011

    Article  PubMed  CAS  Google Scholar 

  • Hiraoka K et al (2006) Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinoma. Br J Cancer 94:275–280

    Article  PubMed  CAS  Google Scholar 

  • Howell A, Landberg G, Bergh J (2009) Breast tumour stroma is a prognostic indicator and target for therapy. Breast Cancer Res 11(Suppl 3):S16

    Article  PubMed  Google Scholar 

  • Hu M et al (2005) Distinct epigenetic changes in the stromal cells of breast cancers. Nat Genet 37:899–905

    Article  PubMed  CAS  Google Scholar 

  • Hu M et al (2008) Regulation of in situ to invasive breast carcinoma transition. Cancer Cell 13:394–406

    Article  PubMed  CAS  Google Scholar 

  • Huang S, Ingber DE (2005) Cell tension, matrix mechanics, and cancer development. Cancer Cell 8:175–176

    Article  PubMed  CAS  Google Scholar 

  • Hurd TC et al (2007) Plasminogen activator system localization in 60 cases of ductal carcinoma in situ. Ann Surg Oncol 14:3117–3124

    Article  PubMed  Google Scholar 

  • Husemann Y et al (2008) Systemic spread is an early step in breast cancer. Cancer Cell 13:58–68

    Article  PubMed  CAS  Google Scholar 

  • Iyengar P et al (2003) Adipocyte-secreted factors synergistically promote mammary tumorigenesis through induction of anti-apoptotic transcriptional programs and proto-oncogene stabilization. Oncogene 22:6408–6423

    Article  PubMed  CAS  Google Scholar 

  • Iyengar P et al (2005) Adipocyte-derived collagen VI affects early mammary tumor progression in vivo, demonstrating a critical interaction in the tumor/stroma microenvironment. J Clin Invest 115:1163–1176

    PubMed  CAS  Google Scholar 

  • Jain RK (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307:58–62

    Article  PubMed  CAS  Google Scholar 

  • Jeffers M, Rong S, Anver M, Vande Woude GF (1996a) Autocrine hepatocyte growth factor/scatter factor-Met signaling induces transformation and the invasive/metastastic phenotype in C127 cells. Oncogene 13:853–856

    CAS  Google Scholar 

  • Jeffers M, Rong S, Woude GF (1996b) Hepatocyte growth factor/scatter factor-Met signaling in tumorigenicity and invasion/metastasis. J Mol Med 74:505–513

    Article  CAS  Google Scholar 

  • Jordan VC, Brodie AM (2007) Development and evolution of therapies targeted to the estrogen receptor for the treatment and prevention of breast cancer. Steroids 72:7–25

    Article  PubMed  CAS  Google Scholar 

  • Joyce JA (2005) Therapeutic targeting of the tumor microenvironment. Cancer Cell 7:513–520

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Karin M (2009) NF-kappaB as a critical link between inflammation and cancer. Cold Spring Harb Perspect Biol 1:a000141

    Article  PubMed  CAS  Google Scholar 

  • Karnoub AE et al (2007) Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 449:557–563

    Article  PubMed  CAS  Google Scholar 

  • Kass L, Erler JT, Dembo M, Weaver VM (2007) Mammary epithelial cell: influence of extracellular matrix composition and organization during development and tumorigenesis. Int J Biochem Cell Biol 39:1987–1994

    Article  PubMed  CAS  Google Scholar 

  • Knutson KL, Disis ML (2005) Tumor antigen-specific T helper cells in cancer immunity and immunotherapy. Cancer Immunol Immunother 54:721–728

    Article  PubMed  CAS  Google Scholar 

  • Kurose K et al (2002) Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas. Nat Genet 32:355–357

    Article  PubMed  CAS  Google Scholar 

  • Ladoire S et al (2008) Pathologic complete response to neoadjuvant chemotherapy of breast carcinoma is associated with the disappearance of tumor-infiltrating foxp3+ regulatory T cells. Clin Cancer Res 14:2413–2420

    Article  PubMed  CAS  Google Scholar 

  • Lafkas D, Trimis G, Papavassiliou AG, Kiaris H (2008) P53 mutations in stromal fibroblasts sensitize tumors against chemotherapy. Int J Cancer 123:967–971

    Article  PubMed  CAS  Google Scholar 

  • Lan RY, Ansari AA, Lian ZX, Gershwin ME (2005) Regulatory T cells: development, function and role in autoimmunity. Autoimmun Rev 4:351–363

    Article  PubMed  CAS  Google Scholar 

  • Landskroner-Eiger S et al (2009) Proangiogenic contribution of adiponectin toward mammary tumor growth in vivo. Clin Cancer Res 15:3265–3276

    Article  PubMed  CAS  Google Scholar 

  • Leek RD, Harris AL (2002) Tumor-associated macrophages in breast cancer. J Mammary Gland Biol Neoplasia 7:177–189

    Article  PubMed  Google Scholar 

  • Lewis CE, Pollard JW (2006) Distinct role of macrophages in different tumor microenvironments. Cancer Res 66:605–612

    Article  PubMed  CAS  Google Scholar 

  • Lewis GD et al (1993) Differential responses of human tumor cell lines to anti-p185HER2 monoclonal antibodies. Cancer Immunol Immunother 37:255–263

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Lin EY, Gouon-Evans V, Nguyen AV, Pollard JW (2002) The macrophage growth factor CSF-1 in mammary gland development and tumor progression. J Mammary Gland Biol Neoplasia 7:147–162

    Article  PubMed  Google Scholar 

  • Lipton A (2008) Emerging role of bisphosphonates in the clinic–antitumor activity and prevention of metastasis to bone. Cancer Treat Rev 34(Suppl 1):S25–30

    Article  PubMed  CAS  Google Scholar 

  • Lu X, Kang Y (2007) Organotropism of breast cancer metastasis. J Mammary Gland Biol Neoplasia 12:153–162

    Article  PubMed  Google Scholar 

  • Ma XJ, Dahiya S, Richardson E, Erlander M, Sgroi DC (2009) Gene expression profiling of the tumor microenvironment during breast cancer progression. Breast Cancer Res 11:R7

    Article  PubMed  CAS  Google Scholar 

  • Manabe Y, Toda S, Miyazaki K, Sugihara H (2003) Mature adipocytes, but not preadipocytes, promote the growth of breast carcinoma cells in collagen gel matrix culture through cancer-stromal cell interactions. J Pathol 201:221–228

    Article  PubMed  Google Scholar 

  • Mantovani A, Sozzani S, Locati M, Allavena P, Sica A (2002) Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23:549–555

    Article  PubMed  CAS  Google Scholar 

  • Mantovani A et al (2004a) Chemokines in the recruitment and shaping of the leukocyte infiltrate of tumors. Semin Cancer Biol 14:155–160

    Article  CAS  Google Scholar 

  • Mantovani A et al (2004b) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25:677–686

    Article  CAS  Google Scholar 

  • Martin-Orozco N et al (2009) T helper 17 cells promote cytotoxic T cell activation in tumor immunity. Immunity 31:787–798

    Article  PubMed  CAS  Google Scholar 

  • Matsushima K, Larsen CG, DuBois GC, Oppenheim JJ (1989) Purification and characterization of a novel monocyte chemotactic and activating factor produced by a human myelomonocytic cell line. J Exp Med 169:1485–1490

    Article  PubMed  CAS  Google Scholar 

  • Mauro L et al (2007) Evidences that leptin up-regulates E-cadherin expression in breast cancer: effects on tumor growth and progression. Cancer Res 67:3412–3421

    Article  PubMed  CAS  Google Scholar 

  • McAllister SS et al (2008) Systemic endocrine instigation of indolent tumor growth requires osteopontin. Cell 133:994–1005

    Article  PubMed  CAS  Google Scholar 

  • Meng S et al (2006) uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues. Proc Natl Acad Sci U S A 103:17361–17365

    Article  PubMed  CAS  Google Scholar 

  • Micke P, Ostman A (2004) Tumour-stroma interaction: cancer-associated fibroblasts as novel targets in anti-cancer therapy? Lung Cancer 45(Suppl 2):S163–75

    Article  Google Scholar 

  • Miki Y, Suzuki T, Sasano H (2007) Controversies of aromatase localization in human breast cancer–stromal versus parenchymal cells. J Steroid Biochem Mol Biol 106:97–101

    Article  PubMed  CAS  Google Scholar 

  • Mishra PJ et al (2008) Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells. Cancer Res 68:4331–4339

    Article  PubMed  CAS  Google Scholar 

  • Moinfar F et al (2000) Concurrent and independent genetic alterations in the stromal and epithelial cells of mammary carcinoma: implications for tumorigenesis. Cancer Res 60:2562–2566

    PubMed  CAS  Google Scholar 

  • Muller A et al (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410:50–56

    Article  PubMed  CAS  Google Scholar 

  • Muranski P et al (2008) Tumor-specific Th17-polarized cells eradicate large established melanoma. Blood 112:362–373

    Article  PubMed  CAS  Google Scholar 

  • Nielsen BS, Rank F, Illemann M, Lund LR, Dano K (2007) Stromal cells associated with early invasive foci in human mammary ductal carcinoma in situ coexpress urokinase and urokinase receptor. Int J Cancer 120:2086–2095

    Article  PubMed  CAS  Google Scholar 

  • Nishimura R, Arima N (2008) Is triple negative a prognostic factor in breast cancer? Breast Cancer 15:303–308

    Article  PubMed  Google Scholar 

  • Orimo A, Weinberg RA (2006) Stromal fibroblasts in cancer: a novel tumor-promoting cell type. Cell Cycle 5:1597–1601

    Article  PubMed  CAS  Google Scholar 

  • Orimo A et al (2005) Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121:335–348

    Article  PubMed  CAS  Google Scholar 

  • Pages F et al (2005) Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 353:2654–2666

    Article  PubMed  CAS  Google Scholar 

  • Paszek MJ et al (2005) Tensional homeostasis and the malignant phenotype. Cancer Cell 8:241–254

    Article  PubMed  CAS  Google Scholar 

  • Patel RR, Sharma CG, Jordan VC (2007) Optimizing the antihormonal treatment and prevention of breast cancer. Breast Cancer 14:113–22

    Article  PubMed  Google Scholar 

  • Perou CM et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752

    Article  PubMed  CAS  Google Scholar 

  • Pontiggia O et al (2009) Establishment of an in vitro estrogen-dependent mouse mammary tumor model: a new tool to understand estrogen responsiveness and development of tamoxifen resistance in the context of stromal-epithelial interactions. Breast Cancer Res Treat 116:247–255

    Article  PubMed  CAS  Google Scholar 

  • Provenzano PP et al (2006) Collagen reorganization at the tumor-stromal interface facilitates local invasion. BMC Med 4:38

    Article  PubMed  CAS  Google Scholar 

  • Provenzano PP et al (2008) Collagen density promotes mammary tumor initiation and progression. BMC Med 6:11

    Article  PubMed  CAS  Google Scholar 

  • Quemener C et al (2007) Extracellular matrix metalloproteinase inducer up-regulates the urokinase-type plasminogen activator system promoting tumor cell invasion. Cancer Res 67:9–15

    Article  PubMed  CAS  Google Scholar 

  • Rakha EA, Ellis IO (2009) Triple-negative/basal-like breast cancer: review. Pathology 41:40–47

    Article  PubMed  Google Scholar 

  • Rong S et al (1993) Tumorigenesis induced by coexpression of human hepatocyte growth factor and the human met protooncogene leads to high levels of expression of the ligand and receptor. Cell Growth Differ 4:563–569

    PubMed  CAS  Google Scholar 

  • Rong S, Segal S, Anver M, Resau JH, Vande Woude GF (1994) Invasiveness and metastasis of NIH 3T3 cells induced by Met-hepatocyte growth factor/scatter factor autocrine stimulation. Proc Natl Acad Sci U S A 91:4731–4735

    Article  PubMed  CAS  Google Scholar 

  • Sadlonova A et al (2009) Identification of Molecular Distinctions Between Normal Breast-Associated Fibroblasts and Breast Cancer-Associated Fibroblasts. Cancer Microenviron 2:9–21

    Article  PubMed  CAS  Google Scholar 

  • Santen RJ et al (1997) Estrogen production via the aromatase enzyme in breast carcinoma: which cell type is responsible? J Steroid Biochem Mol Biol 61:267–271

    Article  PubMed  CAS  Google Scholar 

  • Santen RJ et al (1998) Demonstration of aromatase activity and its regulation in breast tumor and benign breast fibroblasts. Breast Cancer Res Treat 49 (Suppl 1):S93–99; (discussion S109–19)

    Article  PubMed  CAS  Google Scholar 

  • Santner SJ, Pauley RJ, Tait L, Kaseta J, Santen RJ (1997) Aromatase activity and expression in breast cancer and benign breast tissue stromal cells. J Clin Endocrinol Metab 82:200–208

    Article  PubMed  CAS  Google Scholar 

  • Sappino AP, Skalli O, Jackson B, Schurch W, Gabbiani G (1988) Smooth-muscle differentiation in stromal cells of malignant and non-malignant breast tissues. Int J Cancer 41:707–712

    Article  PubMed  CAS  Google Scholar 

  • Schedin P, Borges V (2009) Breaking down barriers: the importance of the stromal microenvironment in acquiring invasiveness in young women’s breast cancer. Breast Cancer Res 11:102

    Article  PubMed  CAS  Google Scholar 

  • Sharma M et al (2009) Analysis of stromal signatures in the tumor microenvironment of ductal carcinoma in situ. Breast Cancer Res Treat 123(2):397–404

    Google Scholar 

  • Sica A et al (2008) Macrophage polarization in tumour progression. Semin Cancer Biol 18:349–355

    Google Scholar 

  • Singer CF et al (2008) Differential gene expression profile in breast cancer-derived stromal fibroblasts. Breast Cancer Res Treat 110:273–281

    Article  PubMed  CAS  Google Scholar 

  • Sorlie T et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98:10869–10874

    Article  PubMed  CAS  Google Scholar 

  • Steinman L (2007) A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage. Nat Med 13:139–145

    Article  PubMed  CAS  Google Scholar 

  • Su X et al (2010) Tumor microenvironments direct the recruitment and expansion of human Th17 cells. J Immunol 184:1630–1641

    Article  PubMed  CAS  Google Scholar 

  • Suzuki T et al (2008) Aromatase in human breast carcinoma as a key regulator of intratumoral sex steroid concentrations. Endocr J 55:455–463

    Article  PubMed  CAS  Google Scholar 

  • Teschendorff AE, Naderi A, Barbosa-Morais NL, Caldas C (2006) PACK: Profile Analysis using Clustering and Kurtosis to find molecular classifiers in cancer. Bioinformatics 22:2269–2275

    Article  PubMed  CAS  Google Scholar 

  • Teschendorff AE, Miremadi A, Pinder SE, Ellis IO, Caldas C (2007) An immune response gene expression module identifies a good prognosis subtype in estrogen receptor negative breast cancer. Genome Biol 8:R157

    Article  PubMed  CAS  Google Scholar 

  • Tesmer LA, Lundy SK, Sarkar S, Fox DA (2008) Th17 cells in human disease. Immunol Rev 223:87–113

    Article  PubMed  CAS  Google Scholar 

  • Tokes AM et al (2009) Stromal matrix protein expression following preoperative systemic therapy in breast cancer. Clin Cancer Res 15:731–739

    Article  PubMed  CAS  Google Scholar 

  • Trimboli AJ et al (2009) Pten in stromal fibroblasts suppresses mammary epithelial tumours. Nature 461:1084–1091

    Article  PubMed  CAS  Google Scholar 

  • van ’t Veer LJ et al (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415:530–536

    Article  Google Scholar 

  • van de Vijver, M.J. et al (2002) A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347:1999–2009

    Article  PubMed  Google Scholar 

  • Wang W et al (2002) Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling. Cancer Res 62:6278–6288

    PubMed  CAS  Google Scholar 

  • Weigelt B, Lo AT, Park CC, Gray JW, Bissell MJ (2010) HER2 signaling pathway activation and response of breast cancer cells to HER2-targeting agents is dependent strongly on the 3D microenvironment. Breast Cancer Res Treat 122:35–43

    Article  PubMed  CAS  Google Scholar 

  • White DE et al (2004) Targeted disruption of beta1-integrin in a transgenic mouse model of human breast cancer reveals an essential role in mammary tumor induction. Cancer Cell 6:159–170

    Article  PubMed  CAS  Google Scholar 

  • Wu S et al (2009) A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17T cell responses. Nat Med 15:1016–1022

    Article  PubMed  CAS  Google Scholar 

  • Wyckoff J et al (2004) A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res 64:7022–7029

    Article  PubMed  CAS  Google Scholar 

  • Wyckoff JB et al (2007) Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Res 67:2649–2656

    Article  PubMed  CAS  Google Scholar 

  • Xu R, Boudreau A, Bissell MJ (2009) Tissue architecture and function: dynamic reciprocity via extra- and intra-cellular matrices. Cancer Metastasis Rev 28:167–176

    Article  PubMed  Google Scholar 

  • Yu H, Pardoll D, Jove R (2009) STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer 9:798–809

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Many studies have addressed the various components of the breast cancer stroma and their interactions with each other, and with the tumor per se. Therefore space limitations render it impossible to adequately acknowledge all of the contributions by the many key individuals and groups who have studied different aspects of this research area in detail, and have made it necessary to refer the reader to reviews in many cases where the primary literature is very large. The authors apologize in advance for any omissions.

Work on this area in our group has been supported by grants from multiple agencies, including the Québec Breast Cancer Foundation, Genome Canada–Génome Québec, Valorisation-Recherche Québec, the Fonds de la Récherche en Santé du Québec, the Canadian Institutes of Health Research and the Terry Fox Foundation (to M.P.). M.P. holds the Diane and Sal Guerrera Chair in Cancer Genetics at McGill University.

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Authors and Affiliations

  1. Rosalind & Morris Goodman Cancer Research Centre, McGill University, 1160 Ave. des Pins O., H3A 1A3, Montreal, QC, Canada

    Nicholas R. Bertos & Morag Park

  2. Department of Medicine, McGill University, Montreal, QC, Canada

    Nicholas R. Bertos & Morag Park

  3. Departments of Oncology and Biochemistry, McGill University, Montreal, QC, Canada

    Morag Park

  4. Department of Medicine, McGill University Health Centre, Montreal, QC, Canada

    Morag Park

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  1. Nicholas R. Bertos
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  2. Morag Park
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Correspondence to Nicholas R. Bertos .

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Editors and Affiliations

  1. Centre for Genomic Regulation, N/A, Barcelona, N/A, Spain

    Julia V. Burnier

  2. , Ophthalmology, Pathology, Medicine & Onc, McGill University Health Centre, University Street 3775, Montreal, H3A 2B4, Québec, Canada

    Miguel N. Burnier, Jr.

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Bertos, N., Park, M. (2013). Role of Stroma in Disease Progression. In: Burnier, J., Burnier, Jr., M. (eds) Experimental and Clinical Metastasis. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3685-0_10

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