Top

Published in:

01-12-2009 | Short communication

Breast tumour stroma is a prognostic indicator and target for therapy

Authors: Anthony Howell, Goran Landberg, Jonas Bergh

Published in: Breast Cancer Research | Special Issue 3/2009

Excerpt

The development of the breast is exquisitely sensitive to interactions between the epithelium and stroma. Experimental evidence indicates that a reduction in signalling between any of the stromal cell types (fibroblasts, macrophages, endothelial cells and adipocytes) results in reduced or absent breast development [1], although all interactions appear to be orchestrated by the epithelial cell oestrogen receptor alpha [2]. The epithelial-stromal interactions that occur in tumours are less well characterised but there is no doubt there is expansion of the stroma as well as of the epithelium during tumour development [3, 4]. Recent data indicate that the prognosis after breast cancer diagnosis relates to stromal type, and experimental and clinical studies directed at modifying the stroma (for example, angiogenesis inhibitors) suggest that the stroma is a target for therapy that is worthy of further exploration …

Howell A, Sims AH, Ong KR, Harvie MN, Evans DG, Clarke RB: Mechanisms of disease: prediction and prevention of breast cancer-cellular and molecular interactions. Natl Clin Pract Oncol. 2005, 2: 635-646. 10.1038/ncponc0361.CrossRef

Mallepell S, Krust A, Chambon P, Brisken C: Paracrine signalling through the epithelial estrogen receptor alpha is required for proliferation and morphogenesis in the mammary gland. Proc Natl Acad Sci USA. 2006, 103: 2196-2201. 10.1073/pnas.0510974103.CrossRefPubMedPubMedCentral

Wellings SR, Jensen HM, Marcum RG: An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions. J Natl Cancer Inst. 1975, 55: 231-273.PubMed

Lee S, Mohsin SK, Mao S, Hilsenbeck SG, Medina D, Allred DC: Hormones, receptors and growth in hyperplastic enlarged lobular units: early potential precursors of breast cancer. Breast Cancer Res. 2006, 8: R6-10.1186/bcr1367.CrossRefPubMed

Ma XJ, Dahiya S, Richardson E, Erlander M, Sgroi DC: Gene expression profiling of the tumor microenvironment during breast cancer progression. Breast Cancer Res. 2009, 11: R7-10.1186/bcr2222.CrossRefPubMedPubMedCentral

Casey T, Bond J, Tighe S, Hunter T, Lintault L, Patel O, Eneman J, Crocker A, White J, Tessitore J, Stanley M, Harlow S, Weaver D, Muss H, Plaut K: Molecular signatures suggest a major role for stromal cells in development of invasive breast cancer. Breast Cancer Res Treat. 2009, 114: 47-62. 10.1007/s10549-008-9982-8.CrossRefPubMed

Dvorak HF: Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986, 315: 1650-1659. 10.1056/NEJM198612253152606.CrossRefPubMed

Chang HY, Sneddon JB, Alizadeh AA, Sood R, West RB, Montgomery K, Chi JT, Rijn van de M, Botstein D, Brown PO: Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds. PLoS Biol. 2004, 2: E7-10.1371/journal.pbio.0020007.CrossRefPubMedPubMedCentral

Chang HY, Nuyten DS, Sneddon JB, Hastie T, Tibshirani R, Sørlie T, Dai H, He YD, van't Veer LJ, Bartelink H, Rijn van de M, Brown PO, Vijver van de MJ: Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival. Proc Natl Acad Sci USA. 2005, 102: 3738-3743. 10.1073/pnas.0409462102.CrossRefPubMedPubMedCentral

10.

Finak G, Bertos N, Pepin F, Sadekova S, Souleimanova M, Zhao H, Chen H, Omeroglu G, Meterissian S, Omeroglu A, Hallett M, Park M: Stromal gene expression predicts clinical outcome in breast cancer. Nat Med. 2008, 14: 518-527. 10.1038/nm1764.CrossRefPubMed

11.

Wennmalm K, Ostman A, Bergh J: Stromal signature identifies basal breast cancer. Nat Med. 2009, 15: 237-238. 10.1038/nm0309-237.CrossRefPubMed

12.

Bergamaschi A, Tagliabue E, Sørlie T, Naume B, Triulzi T, Orlandi R, Russness HG, Nesland JM, Tammi R, Auvininen P, Kosma VM, Menard S, Borresen-Dale AL: Extracelluar matrix signature identifies breast cancer subgroups with diferent clinical outcome. J Pathol. 2008, 214: 257-267. 10.1002/path.2278.CrossRef

13.

Farmer P, Bonnefoi H, Anderle P, Cameron D, Wirapati P, Becette V, André S, Piccart M, Campone M, Brain E, Macgrogan G, Petit T, Jassem J, Bibeau F, Blot E, Bogaerts J, Aguet M, Bergh J, Iggo R, Delorenzi M: A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer. Nat Med. 2009, 15: 68-74. 10.1038/nm.1908.CrossRefPubMed

14.

Witkiewicz AK, Dasgupta A, Sotgia F, Mercier I, Pestell RG, Sabel M, Kleer CG, Brody JR, Lisanti MP: An absence of stromal caveolin-1 expression predicts early tumor recurrence and poor clinical outcome in human breast cancers. Am J Pathol. 2009, 174: 2023-2034. 10.2353/ajpath.2009.080873.CrossRefPubMedPubMedCentral

15.

Witkiewicz AK, Dasgupta A, Nguyen KH, Liu C, Kovatich AJ, Schwartz GF, Pestell RG, Sotgia F, Rui H, Lisanti MP: Stromal caveolin-1 levels predict early DCIS progression to invasive breast cancer. Cancer Biol Ther. 2009, 8: 1071-1079. 10.4161/cbt.8.11.8874.CrossRefPubMed

16.

Sloan EK, Ciocca DR, Pouliot N, Natoli A, Restall C, Henderson MA, Fanelli MA, Cuello-Carrión FD, Gago FE, Anderson RL: Stromal cell expression of caveolin-1 predicts outcome in breast cancer. Am J Pathol. 2009, 174: 2035-2043. 10.2353/ajpath.2009.080924.CrossRefPubMedPubMedCentral

17.

Koleske AJ, Baltimore D, Lisanti MP: Reduction of caveolin and caveolae in oncogenically transformed cells. Proc Natl Acad Sci USA. 1995, 92: 1381-1385. 10.1073/pnas.92.5.1381.CrossRefPubMedPubMedCentral

18.

Engelman JA, Wykoff CC, Yasuhara S, Song KK, Okamoto T, Lisanti MP: Recombinant expression of caveolin-1 in oncogeneity transformed cells abrogates anchorage-independent growth. J Biol Chem. 1997, 272: 16374-16381. 10.1074/jbc.272.26.16374.CrossRefPubMed

19.

Cuzick J, Warwick J, Pinney L, Warren R, Cawthorn S, Howell A, Duffy S: Change in breast density as a biomarker of breast cancer risk reduction results from IBIS I [abstract]. San Antonio Breast Cancer Symposium; 10-14. 2008, [http://www.abstracts2view.com/sabcs/]December

20.

Hattar R, Maller O, McDaniel S, Hansen KC, Hedman KJ, Lyons TR, Lucia S, Wilson RS, Schedin P: Tamoxifen induces pleiotrophic changes in mammary stroma resulting in extra-cellular matrix that suppresses transformed phenotypes. Breast Cancer Res. 2009, 11: R5-10.1186/bcr2220.CrossRefPubMedPubMedCentral

21.

McAllister SS, Gifford AM, Greiner AL, Kelleher SP, Saelzler MP, Ince TA, Reinhardt F, Harris LN, Hylander BL, Repasky EA, Weinberg RA: Systemic endocrine instigation of indolent tumor growth requires osteopontin. Cell. 2008, 133: 994-1005. 10.1016/j.cell.2008.04.045.CrossRefPubMedPubMedCentral

22.

Erler JT, Bennewith KL, Cox TR, Lang G, Bird D, Koong A, Le Q-T, Giaccia AJ: Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell. 2009, 15: 35-44. 10.1016/j.ccr.2008.11.012.CrossRefPubMedPubMedCentral

23.

Banka CL, Lung CV, Nguyen MTN, Pakchoian AJ, Mueller BM, Eliceiri BP: Estrogen induces lung metastasis through a host compartment-specific response. Cancer Res. 2006, 66: 3667-3672. 10.1158/0008-5472.CAN-05-4416.CrossRefPubMed

24.

Gupta PB, Proia D, Cingoz O, Weremowicz J, Naber SP, Weinberg RA, Kuperwasser C: Systemic stromal effects of estrogen promote the growth of estrogen receptor-negative cancers. Cancer Res. 2007, 67: 2062-2071. 10.1158/0008-5472.CAN-06-3895.CrossRefPubMed

25.

Joyce JA, Pollard JW: Microenvironment regulation of metastasis. Nat Rev. 2009, 9: 239-252. 10.1038/nrc2618.CrossRef

26.

Psaila B, Lyden D: The metastatic niche: adapting the foreign soil. Nat Rev. 2009, 9: 285-293. 10.1038/nrc2621.CrossRef

27.

Broom RJ, Tang PA, Simmons C, Bordeleau L, Mulligan AM, O'Malley FP, Miller N, Andrulis IL, Brenner DM, Clemons MJ: Changes in estrogen receptor, progesterone receptor and Her-2/neu status with time: discordance rates between primary and metastatic breast cancer. Anticancer Res. 2009, 29: 1557-1562.PubMed

28.

Gadea BB, Joyce JA: Tumour-host interactions: implications for developing anti-cancer therapies. Expert Rev Mol Med. 2006, 8: 1-32. 10.1017/S1462399406000172.CrossRefPubMed

29.

Ronnov-Jessen L, Bissell MJ: Breast cancer by proxy: can the microenvironment be both the cause and consequence?. Trends Mol Med. 2009, 15: 5-13. 10.1016/j.molmed.2008.11.001.CrossRefPubMed

30.

Ostman A, Augsten M: Cancer-associated fibroblasts and tumour growth-bystanders turning into key players. Curr Opin Genet Dev. 2009, 19: 67-73. 10.1016/j.gde.2009.01.003.CrossRefPubMed

31.

Morton AR, Cantrill JA, Pillai GV, McMahon A, Anderson DC, Howell A: Sclerosis of lytic bone metastases after disodium aminohydroxypropylidene bisphosphonate (APD) in patients with breast carcinoma. Br Med J. 1988, 297: 772-773. 10.1136/bmj.297.6651.772.CrossRef

32.

Lebeau AM, Brennen WN, Aggarwal S, Denmeade SR: Targeting the cancer stroma with a fibroblast activation protein-activated promelittin protoxin. Mol Cancer Ther. 2009.

33.

Iwasaki Y, Akari H, Murakami T, Kumakura S, Dewan Z, Yanaka M, Yamamoto N: Efficient inhibition of SDF-1α [GREEK]-mediated chemotaxis and HIV-1 infection by novel CXCR4 antagonists. Cancer Sci. 100: 778-781. 10.1111/j.1349-7006.2009.01104.x.

34.

Luo Y, Zhou H, Kreuger J, Kaplan C, Lee SH, Dolman C, Markowitz D, Wu W, Liu C, Reidfeld RA, Xiang R: Targetting tumour-associated macrophages as a novel strategy against breast cancer. J Clin Invest. 116: 2132-2141. 10.1172/JCI27648.

35.

Garber K: First results for agents targeting cancer-related inflammation. J Natl Cancer Inst. 2009, 101: 1110-1112. 10.1093/jnci/djp266.CrossRefPubMed

36.

Meads MB, Gatenby RA, Dalton WS: Environment-mediated drug resistance: a major contributor to minimal residual disease. Nat Rev. 2009, 9: 665-675. 10.1038/nrc2714.CrossRef

37.

Fritz V, Jorgensen C: Menenchymal stem cells: an emerging tool for cancer targeting and therapy. Curr Stem Cell Res Ther. 2008, 3: 32-42. 10.2174/157488808783489462.CrossRefPubMed

38.

Kucerova L, Altanerova V, Matuskova M, Tyciakova S, Altaner C: Adipose-derived human mesenchymal stem cell mediated prodrug gene therapy. Cancer Res. 2007, 67: 6304-6313. 10.1158/0008-5472.CAN-06-4024.CrossRefPubMed

39.

Shekhar MP, Santner S, Carolin KA, Tait L: Direct involvement of breast tumor fibroblasts in the modulation of tamoxifen sensitivity. Am J Pathol. 2007, 170: 1546-1560. 10.2353/ajpath.2007.061004.CrossRefPubMedPubMedCentral

Title: Breast tumour stroma is a prognostic indicator and target for therapy
Authors: Anthony Howell
Goran Landberg
Jonas Bergh
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: Breast Cancer Research / Issue Special Issue 3/2009
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/bcr2435

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Excerpt

Please log in to get access to this content

Other articles of this Special Issue 3/2009

Radiation impact in breast cancer

The potential of new technologies/approaches. Introduction to Sessions 3 and 4

Who would have thought it! Influence on outcome of radiotherapy, Ki67 and stroma. Introduction to Session 5

Introduction to sessions on guidelines and endocrine therapy, the influence of breast screening on number of mastectomies and the challenge between molecular science and traditional dogma in the treatment of breast cancer. Introduction to Session 6

Controversies in breast cancer: the mammalian target of rapamycin as a target for breast cancer therapy

Underarm antiperspirants/deodorants and breast cancer

Keynote webinar | Spotlight on antibody–drug conjugates in cancer