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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 1/2009

01-03-2009 | Preclinical Study

Molecular signatures suggest a major role for stromal cells in development of invasive breast cancer

Authors: Theresa Casey, Jeffrey Bond, Scott Tighe, Timothy Hunter, Laura Lintault, Osman Patel, Jonathan Eneman, Abigail Crocker, Jeffrey White, Joseph Tessitore, Mary Stanley, Seth Harlow, Donald Weaver, Hyman Muss, Karen Plaut

Published in: Breast Cancer Research and Treatment | Issue 1/2009

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Abstract

Background Breast cancer invasion and metastasis involves both epithelial and stromal changes. Our objective was to delineate the pivotal role stroma plays in invasion by comparing transcriptomes among stromal and epithelial cells in normal tissue and invasive breast cancer. Methods Total RNA was isolated from epithelial and stromal cells that were laser captured from normal breast tissue (n = 5) and invasive breast cancer (n = 28). Gene expression was measured using Affymetrix U133A 2.0 GeneChips. Differential gene expression was evaluated and compared within a model that accounted for cell type (epithelial [E] versus stromal [S]), diagnosis (cancer [C] versus normal [N]) as well as cell type-diagnosis interactions. Results Compared to NE, the CE transcriptome was highly enriched with genes in proliferative, motility and ECM ontologies. Differences in CS and NS transcriptomes suggested that the ECM was being remodeled in invasive breast cancer, as genes were over-represented in ECM and proteolytic ontologies. Genes more highly expressed in CS compared to CE were primarily ECM components or were involved in the remodeling of ECM, suggesting that ECM biosynthesis and remodeling were initiated in the tumor stroma. Conclusion Based on identified molecular cross-talk between the two contiguous cell populations, a mechanistic model that spurs invasion is proposed, that shows breast cancer invasion proceeds through the acquisition of a motile phenotype in tumor epithelial cells and a reactive phenotype in cancer associated fibroblasts.
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Literature
1.
2.
Janda E, Lehmann K, Killisch I, Jechlinger M, Herzig M, Downward J, Beug H, Grunert S (2002) Ras and TGF[beta] cooperatively regulate epithelial cell plasticity and metastasis: dissection of Ras signaling pathways. J Cell Biol 156:299–313PubMedCrossRef
3.
Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2:563–572PubMedCrossRef
4.
Fidler IJ (2003) The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer 3:453–458PubMedCrossRef
5.
6.
Tlsty TD, Hein PW (2001) Know thy neighbor: stromal cells can contribute oncogenic signals. Curr Opin Genet Dev 11:54–59PubMedCrossRef
7.
de Visser K, Korets L, Coussens L (2005) De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Cancer Res 7:411–423
8.
Kim K, Li B, Winer J, Armanini M, Gillett N, Phillips H, Ferrara N (1993) Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362:841–844PubMedCrossRef
9.
Condeelis J, Pollard JW (2006) Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 124:263–266PubMedCrossRef
10.
Noel A, Foidart J-M (1998) The role of stroma in breast carcinoma growth in vivo. J Mammary Gland Biol Neoplasia V3:215–225CrossRef
11.
Tuxhorn JA, McAlhany SJ, Dang TD, Ayala GE, Rowley DR (2002) Stromal cells promote angiogenesis and growth of human prostate tumors in a differential reactive stroma (DRS) xenograft model. Cancer Res 62:3298–3307PubMed
12.
Mueller MM, Fusenig NE (2004) friends or foes- bipolar effects of the tumour stroma in cancer. Nat Rev Cancer 4:839–849PubMedCrossRef
13.
14.
15.
Roepman P, de Koning E, van Leenen D, de Weger R, Kummer JA, Slootweg P, Holstege F (2006) Dissection of a metastatic gene expression signature into distinct components. Genome Biol 7:R117PubMedCrossRef
16.
Yamabuki T, Daigo Y, Kato T, Hayama S, Tsunoda T, Miyamoto M, Ito T, Fujita M, Hosokawa M, Kondo S, Nakamura Y (2006) Genome-wide gene expression profile analysis of esophageal squamous cell carcinomas. Int J Oncol 28(6):1375–1384
17.
Nakamura N, Iijima T, Mase K, Furuya S, Kano J, Morishita Y, Noguchi M (2004) Phenotypic differences of proliferating fibroblasts in the stroma of lung adenocarcinoma and normal bronchus tissue. Cancer Sci 95:226–232PubMedCrossRef
18.
Finak G, Sadekova S, Pepin F, Hallett M, Meterissian S, Halwani F, Khetani K, Souleimanova M, Zabolotny B, Omeroglu A, Park M (2006) Gene expression signatures of morphologically normal breast tissue identify basal-like tumors. Breast Cancer Res 8:R58PubMedCrossRef
19.
Elston CW, Ellis IO (1991) Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19:403–410PubMedCrossRef
20.
21.
Gentleman R, Carey V, Bates D, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, Hornik K, Hothorn T, Huber W, Iacus S, Irizarry R, Leisch F, Li C, Maechler M, Rossini A, Sawitzki G, Smith C, Smyth G, Tierney L, Yang J, Zhang J (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5:R80PubMedCrossRef
22.
Irizarry RA, Bolstad BM, Collin F, Cope LM, Hobbs B, Speed TP (2003) Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res 31:e15PubMedCrossRef
23.
Bolstad BM, Irizarry RA, Astrand M, Speed TP (2003) A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19:185–193PubMedCrossRef
24.
Falcon S, Gentleman R (2007) Using GOstats to test gene lists for GO term association. Bioinformatics 23:257–258PubMedCrossRef
25.
Marisa MF, Jérôme T, Marie-Ange D, Ilaria Taddei-De La H, Jean Paul T, Marina AG (2005) Myoepithelial cells in the control of mammary development and tumorigenesis: data from genetically modified mice. J Mammary Gland Biol Neoplasia 10:211–219CrossRef
26.
Woodward TL, Mienaltowski AS, Modi RR, Bennett JM, Haslam SZ (2001) Fibronectin and the {{alpha}}5{beta}1 integrin are under developmental and ovarian steroid regulation in the normal mouse mammary gland. Endocrinology 142:3214–3222PubMedCrossRef
27.
Pujuguet P, Simian M, Liaw J, Timpl R, Werb Z, Bissell MJ (2000) Nidogen-1 regulates laminin-1-dependent mammary-specific gene expression. J Cell Sci 113:849–858PubMed
28.
Nakano S, Iyama K, Ogawa M, Yoshioka H, Sado Y, Oohashi T, Ninomiya Y, (1999) Differential tissular expression and localization of type IV collagen alpha1(IV), alpha2(IV), alpha5(IV), and alpha6(IV) chains and their mRNA in normal breast and in benign and malignant breast tumors. Lab Invest 79:281–292PubMed
29.
Silberstein GB, Daniel CW (1987) Reversible inhibition of mammary gland growth by transforming growth factor-beta. Science 237:291–293PubMedCrossRef
30.
Hu Z, Fan C, Oh DS, Marron JS, He X, Qaqish BF, Livasy C, Carey LA, Reynolds E, Dressler L, Nobel A, Parker J, Ewend MG, Sawyer LR, Wu J, Liu Y, Nanda R, Tretiakova M, Ruiz Orrico A, Dreher D, Palazzo JP, Perreard L, Nelson E, Mone M, Hansen H, Mullins M, Quackenbush JF, Ellis MJ, Olopade OI, Bernard PS, Perou CM (2006) The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 7:96PubMedCrossRef
31.
de Jong JS, van Diest PJ, Baak JP (2000) Hot spot microvessel density and the mitotic activity index are strong additional prognostic indicators in invasive breast cancer. Histopathology 36:306–312PubMedCrossRef
32.
de Jong JS, van Diest PJ, Baak JP (2000) Number of apoptotic cells as a prognostic marker in invasive breast cancer. Br J Cancer 82:368–373PubMedCrossRef
33.
Liu S, Edgerton SM, Moore DH 2nd, Thor AD (2001) Measures of cell turnover (proliferation and apoptosis) and their association with survival in breast cancer. Clin Cancer Res 7:1716–1723PubMed
34.
Mori I, Yang Q, Kakudo K (2002) Predictive and prognostic markers for invasive breast cancer. Pathol Int 52:186–194PubMedCrossRef
35.
Srinivas P, Abraham E, Ahamed I, Madhavan M, Vijayalakshmi NR, Nair MK, Balaram P (2002) Apoptotic index: use in predicting recurrence in breast cancer patients. J Exp Clin Cancer Res 21:233–238PubMed
36.
Vakkala M, Lahteenmaki K, Raunio H, Paakko P, Soini Y (1999) Apoptosis during breast carcinoma progression. Clin Cancer Res 5:319–324PubMed
37.
Abba M, Drake J, Hawkins K, Hu Y, Sun H, Notcovich C, Gaddis S, Sahin A, Baggerly K, Aldaz C (2004) Transcriptomic changes in human breast cancer progression as determined by serial analysis of gene expression. Breast Cancer Res 6:R499–R519PubMedCrossRef
38.
Grigoriadis A, Mackay A, Reis-Filho J, Steele D, Iseli C, Stevenson B, Jongeneel CV, Valgeirsson H, Fenwick K, Iravani M, Leao M, Simpson A, Strausberg R, Jat P, Ashworth A, Neville AM, O’Hare M (2006) Establishment of the epithelial-specific transcriptome of normal and malignant human breast cells based on MPSS and array expression data. Breast Cancer Res 8:R56PubMedCrossRef
39.
Turashvili G, Bouchal J, Baumforth K, Wei W, Dziechciarkova M, Ehrmann J, Klein J, Fridman E, Skarda J, Srovnal J, Hajduch M, Murray P, Kolar Z (2007) Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysis. BMC Cancer 7:55
40.
Folgueira M, Brentani H, Katayama M, Patrão D, Carraro D, Mourão Netto M, Barbosa E, Caldeira J, Abreu A, Lyra E, Kaiano J, Mota L, Campos A, Maciel M, Dellamano M, Caballero O, Brentani M (2006) Gene expression profiling of clinical stages II and III breast cancer. Braz J Med Biol Res 39:1101–1113PubMedCrossRef
41.
Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale A-L, Brown PO, Botstein D (2000) Molecular portraits of human breast tumours. Nature 406:747–752PubMedCrossRef
42.
Mesnil M, Crespin S, Avanzo J-L, Zaidan-Dagli M-L (2005) Defective gap junctional intercellular communication in the carcinogenic process. Biochim Biophys Acta 1719:125–145PubMedCrossRef
43.
Stadler CR, Knyazev P, Bange J, Ullrich A (2006) FGFR4 GLY388 isotype suppresses motility of MDA-MB-231 breast cancer cells by EDG-2 gene repression. Cell Signal 18:783–794PubMedCrossRef
44.
Friedl P, Wolf K (2003) Proteolytic and non-proteolytic migration of tumour cells and leucocytes. Biochem Soc Symp 70:277–285PubMed
45.
Clark EA, Goiub TR, Lander ES, Hynes RO (2000) Genomic analysis of metastasis reveals an essential role for RhoC. Nature 406:532–535PubMedCrossRef
46.
Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordon-Cardo C, Guise TA, Massague J (2003) A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3:537–549PubMedCrossRef
47.
Minn AJ, Gupta GP, Siegel PM, Bos PD, Shu W, Giri DD, Viale A, Olshen AB, Gerald WL, Massague J (2005) Genes that mediate breast cancer metastasis to lung. Nature 436:518–524PubMedCrossRef
48.
Bradshaw A, Sage E (2001) SPARC, a matricellular protein that functions in cellular differentiation and tissue response to injury. J Clin Invest 107:1049–1054PubMedCrossRef
49.
Barth PJ, Moll R, Ramaswamy A (2005) Stromal remodeling and SPARC (secreted protein acid rich in cysteine) expression in invasive ductal carcinomas of the breast. Virchows Arch 446:532–536PubMedCrossRef
50.
Robinson S, Silberstein G, Daniel CW (1992) Evidence supporting a role for TGF-beta isoforms in growth regulation and functional differentiation of the mouse mammary gland. In: Mechanisms regulating lactation and infant nutrient utilization. Wiley-Liss, Inc, New York, pp 43–52
51.
Faler B, Macsata R, Plummer D, Mishra L, Sidawy A (2006) Transforming growth factor-beta and wound healing. Perspect Vasc Surg Endovasc Ther 18:55–62PubMedCrossRef
52.
O’Kane S, Ferguson MWJ (1997) Transforming growth factor [beta]s and wound healing. Int J Biochem Cell Biol 29:63–78PubMedCrossRef
53.
54.
Fleisch MC, Maxwell CA, Barcellos-Hoff M-H (2006) The pleiotropic roles of transforming growth factor beta in homeostasis and carcinogenesis of endocrine organs. Endocrinology 13:379–400
55.
Muraoka-Cook RS, Dumont N, Arteaga CL (2005) Dual role of transforming growth factor beta in mammary tumorigenesis and metastatic progression. Clin Cancer Res 11:937s–943sPubMed
56.
Roberts A, Wakefield L (2003) The two faces of transforming growth factor beta in carcinogenesis. Proc Natl Acad Sci USA 100:8621–8623PubMedCrossRef
57.
Minond D, Lauer-Fields JL, Cudic M, Overall CM, Pei D, Brew K, Moss ML, Fields GB (2007) Differentiation of secreted and membrane-type matrix metalloproteinase activities based on substitutions and interruptions of triple-helical sequences. Biochemistry 46(12):3724–3733
58.
Merrell MA, Ilvesaro JM, Lehtonen N, Sorsa T, Gehrs B, Rosenthal E, Chen D, Shackley B, Harris KW, Selander KS (2006) Toll-like receptor 9 agonists promote cellular invasion by increasing matrix metalloproteinase activity. Mol Cancer Res 4:437–447PubMedCrossRef
59.
Leivonen SK, Ala-aho R, Koli K, Grenman R, Peltonen J, Kahari VM (2006) Activation of Smad signaling enhances collagenase-3 (MMP-13) expression and invasion of head and neck squamous carcinoma cells. Oncogene 25:2588–2600PubMedCrossRef
60.
Lafleur M, Drew A, de Sousa E, Blick T, Bills M, Walker E, Williams E, Waltham M, Thompson E (2005) Upregulation of matrix metalloproteinases (MMPs) in breast cancer xenografts: a major induction of stromal MMP-13. Int J Cancer 114:544–554PubMedCrossRef
61.
Andreas MS, Bartosz A, Rolf M, Toshiyuki Y, Mehdorn HM, Janka H-F (2007) Differential expression of matrix metalloproteinases in brain- and bone-seeking clones of metastatic MDA-MB-231 breast cancer cells. J Neurooncol 81:39–48
62.
Luukkaa M, Vihinen P, Kronqvist P, Vahlberg T, Pyrhönen S, Kähäri V, Grénman R (2006) Association between high collagenase-3 expression levels and poor prognosis in patients with head and neck cancer. Head Neck 28:225–234PubMedCrossRef
63.
Garin-Chesa P, Old LJ, Rettig WJ (1990) Cell surface glycoprotein of reactive stromal fibroblasts as a potential antibody target in human epithelial cancers. PNAS 87:7235–7239PubMedCrossRef
64.
Niedermeyer J, Enenkel B, Park JE, Lenter M, Rettig WJ, Damm K, Schnapp A (1998) Mouse fibroblast-activation protein – conserved Fap gene organization and biochemical function as a serine protease. Eur J Biochem 254:650–654PubMedCrossRef
65.
Scanlan MJ, Raj BKM, Calvo B, Garin-Chesa P, Sanz-Moncasi MP, Healey JH, Old LJ, Rettig WJ (1994) Molecular cloning of fibroblast activation protein {alpha}, a member of the serine protease family selectively expressed in stromal fibroblasts of epithelial cancers. Proc Natl Acad Sci USA 91:5657–5661PubMedCrossRef
66.
Park JE, Lenter MC, Zimmermann RN, Garin-Chesa P, Old LJ, Rettig WJ (1999) Fibroblast activation protein, a dual specificity serine protease expressed in reactive human tumor stromal fibroblasts. J Biol Chem 274:36505–36512PubMedCrossRef
67.
Rettig WJ, Garin-Chesa P, Beresford HR, Oettgen HF, Melamed MR, Old LJ (1988) Cell-surface glycoproteins of human sarcomas: differential expression in normal and malignant tissues and cultured cells. Proc Natl Acad Sci USA 85:3110–3114PubMedCrossRef
68.
Tahtis K, Lee F-T, Wheatley JM, Garin-Chesa P, Park JE, Smyth FE, Obata Y, Stockert E, Hall CM, Old LJ, Rettig WJ, Scott AM (2003) Expression and targeting of human fibroblast activation protein in a human skin/severe combined immunodeficient mouse breast cancer xenograft model. Mol Cancer Res 2:729–737
69.
Scott IC, Blitz IL, Pappano WN, Imamura Y, Clark TG, Steiglitz BM, Thomas CL, Maas SA, Takahara K, Cho KWY, Greenspan DS (1999) Mammalian BMP-1/tolloid-related metalloproteinases, including novel family member mammalian tolloid-like 2, have differential enzymatic activities and distributions of expression relevant to patterning and skeletogenesis. Dev Biol 213:283–300PubMedCrossRef
70.
Veitch DP, Nokelainen P, McGowan KA, Nguyen T-T, Nguyen NE, Stephenson R, Pappano WN, Keene DR, Spong SM, Greenspan DS, Findell PR, Marinkovich MP (2003) Mammalian tolloid metalloproteinase, and not matrix metalloprotease 2 or membrane type 1 metalloprotease, processes laminin-5 in keratinocytes and skin. J Biol Chem 278:15661–15668PubMedCrossRef
71.
Ishikawa T, Kamiyama M, Tani-Ishii N, Suzuki H, Ichikawa Y, Hamaguchi Y, Momiyama N, Shimada H (2001) Inhibition of osteoclast differentiation and bone resorption by cathepsin K antisense oligonucleotides. Mol Carcinog 32:84–91PubMedCrossRef
72.
Lipton A (2005) New therapeutic agents for the treatment of bone diseases. Expert Opin Biol Ther 5:817–832PubMedCrossRef
73.
Turk V, Turk B, Guncar G, Turk D, Kos J (2002) Lysosomal cathepsins: structure, role in antigen processing and presentation, and cancer. Adv Enzyme Regul 42:285–303PubMedCrossRef
74.
Gocheva V, Zeng W, Ke D, Klimstra D, Reinheckel T, Peters C, Hanahan D, Joyce JA (2006) Distinct roles for cysteine cathepsin genes in multistage tumorigenesis. Genes Dev 20:543–556PubMedCrossRef
75.
Micke P, Kappert K, Ohshima M, Sundquist C, Scheidl S, Lindahl P, Heldin C-H, Botling J, Ponten F, Ostman A (2007) In situ identification of genes regulated specifically in fibroblasts of human basal cell carcinoma. J Invest Dermatol 127(6):1516–1523
76.
Cockett M, Murphy G, Birch M, O’Connell J, Crabbe T, Millican A, Hart I, Docherty A (1998) Matrix metalloproteinases and metastatic cancer. Biochem Soc Symp 63:295–313PubMed
77.
Twal WO, Czirok A, Hegedus B, Knaak C, Chintalapudi MR, Okagawa H, Sugi Y, Argraves WS (2001) Fibulin-1 suppression of fibronectin-regulated cell adhesion and motility. J Cell Sci 114:4587–4598PubMed
78.
Hayashido Y, Lucas A et al (1998) Estradiol and fibulin-1 inhibit motility of human ovarian- and breast-cancer cells induced by fibronectin. Int J Cancer 75:654–658
79.
Hubmacher D, Tiedemann K, Reinhardt DP, Gerald PS (2006) Fibrillins: from biogenesis of microfibrils to signaling functions. In: Current topics in developmental biology. Academic Press, pp 93–123
80.
Weir M, Oppizzi M, Henry M, Onishi A, Campbell K, Bissell M, Muschler J (2006) Dystroglycan loss disrupts polarity and beta-casein induction in mammary epithelial cells by perturbing laminin anchoring. J Cell Sci 119:4047–4058PubMedCrossRef
81.
Barresi R, Campbell K (2006) Dystroglycan: from biosynthesis to pathogenesis of human disease. J Cell Sci 119:199–207PubMedCrossRef
82.
Young KG, Pinheiro B, Kothary R (2006) A Bpag1 isoform involved in cytoskeletal organization surrounding the nucleus. Exp Cell Res 312:121–134PubMedCrossRef
83.
Roper K, Gregory SL, Brown NH (2002) The ‘Spectraplakins’: cytoskeletal giants with characteristics of both spectrin and plakin families. J Cell Sci 115:4215–4225PubMedCrossRef
84.
Carraway KL, Sweeney C (2006) Co-opted integrin signaling in ErbB2-induced mammary tumor progression. Cancer Cell 10:93–95PubMedCrossRef
85.
Kolch W (2003) Erbin: sorting out ErbB2 receptors or giving Ras a break? Science pe37
86.
Singer C, Kronsteiner N, Marton E, Kubista M, Cullen K, Hirtenlehner K, Seifert M, Kubista E (2002) MMP-2 and MMP-9 expression in breast cancer-derived human fibroblasts is differentially regulated by stromal-epithelial interactions. Br Cancer Res Treat 72:69–77CrossRef
87.
Basset P, Wolf C, Chambon P (1993) Expression of the stromelysin-3 gene in fibroblastic cells of invasive carcinomas of the breast and other human tissues: a review. Br Cancer Res Treat 24:185–193CrossRef
88.
Okada A, Bellocq J, Rouyer N, Chenard M, Rio M, Chambon P, Basset P (1995) Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas. Proc Natl Acad Sci USA 92:2730–2734PubMedCrossRef
89.
Polette M, Gilles C, Marchand V, Lorenzato M, Toole B, Tournier J-M, Zucker S, Birembaut P (1997) Tumor collagenase stimulatory factor (TCSF) expression and localization in human lung and breast cancers. J Histochem Cytochem 45:703–710PubMed
90.
Tang Y, Kesavan P, Nakada MT, Yan L (2004) Tumor-stroma interaction: positive feedback regulation of extracellular matrix metalloproteinase inducer (EMMPRIN) expression and matrix metalloproteinase-dependent generation of soluble EMMPRIN. Mol Cancer Res 2:73–80PubMed
91.
Bhowmick NA, Chytil A, Plieth D, Gorska AE, Dumont N, Shappell S, Washington MK, Neilson EG, Moses HL (2004) TGF-{beta} signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science 303:848–851PubMedCrossRef
92.
Joesting MS, Perrin S, Elenbaas B, Fawell SE, Rubin JS, Franco OE, Hayward SW, Cunha GR, Marker PC (2005) Identification of SFRP1 as a candidate mediator of stromal-to-epithelial signaling in prostate cancer. Cancer Res 65:10423–10430PubMedCrossRef
93.
Ronnov-Jessen L, Petersen OW, Bissell MJ (1996) Cellular changes involved in conversion of normal to malignant breast: importance of the stromal reaction. Physiol Rev 76:69–125PubMed
94.
Barcellos-Hoff MH, Ravani SA (2000) Irradiated mammary gland stroma promotes the expression of tumorigenic potential by unirradiated epithelial cells. Cancer Res 60:1254–1260PubMed
95.
Barcellos-Hoff MH (1993) Radiation-induced transforming growth factor beta and subsequent extracellular matrix reorganization in murine mammary gland. Cancer Res 53:3880–3886PubMed
96.
Cheng N, Bhowmick NA, Chytil A, Gorksa AE, Brown KA, Muraoka R, Arteaga CL, Neilson EG, Hayward SW, Moses HL (2005) Loss of TGF-beta type II receptor in fibroblasts promotes mammary carcinoma growth and invasion through upregulation of TGF-alpha-, MSP- and HGF-mediated signaling networks. Oncogene 24:5053–5068PubMedCrossRef
97.
Moinfar F, Man YG, Arnould L, Bratthauer GL, Ratschek M, Tavassoli FA (2000) Concurrent and independent genetic alterations in the stromal and epithelial cells of mammary carcinoma: implications for tumorigenesis. Cancer Res 60:2562–2566PubMed
98.
Parrott JA, Nilsson E, Mosher R, Magrane G, Albertson D, Pinkel D, Gray JW, Skinner MK (2001) Stromal-epithelial interactions in the progression of ovarian cancer: influence and source of tumor stromal cells. Mol Cell Endocrinol 175:29–39PubMedCrossRef
99.
Fukumura D, Xavier R, Sugiura T, Chen Y, Park E-C, Lu N, Selig M, Nielsen G, Taksir T, Jain RK, Seed B (1998) Tumor induction of VEGF promoter activity in stromal cells. Cell 94:715–725PubMedCrossRef
100.
Radisky E, Radisky D (2007) Stromal induction of breast cancer: inflammation and invasion. Rev Endocr Metab Disord 8(3):279–287
101.
Condeelis J, Segall JE (2003) Intravital imaging of cell movement in tumours. Nat Rev Cancer 3:921–930PubMedCrossRef
102.
Porter D, Krop I, Nasser S, Sgroi D, Kaelin C, Marks J, Riggins G, Polyak K (2001) A SAGE (Serial Analysis of Gene Expression) view of breast tumor progression. Cancer Res 61:5697–5702PubMed
103.
Elston CW, Ellis IO (2002) Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. C. W. Elston & I. O. Ellis. Histopathology 1991; 19:403–410. Histopathology 41:151
Metadata
Title
Molecular signatures suggest a major role for stromal cells in development of invasive breast cancer
Authors
Theresa Casey
Jeffrey Bond
Scott Tighe
Timothy Hunter
Laura Lintault
Osman Patel
Jonathan Eneman
Abigail Crocker
Jeffrey White
Joseph Tessitore
Mary Stanley
Seth Harlow
Donald Weaver
Hyman Muss
Karen Plaut
Publication date
01-03-2009
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2009
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-008-9982-8

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