Skip to main content

Advertisement

SpringerLink
Log in

Tumour–stroma interactions in carcinogenesis: Basic aspects and perspectives

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

In contrast to the conventional notion regarding tumour development as a cell autonomous process in which the major participants were the cancer cells, increasing evidence attributes important role in the stromal components, namely fibroblasts, and view the tumour as a heterogenous mixture of different cell types. These different types of cells, being cancer cells, fibroblasts, endothelial cells, and others, interact reciprocally and play an almost equally important role in the manifestation of certain aspects of the malignant phenotype. The elucidation of the mechanistic base of such interactions, besides the contribution to understand fundamental aspects of tumour cell biology, promises important applications in diagnosis, prognosis and therapy of the disease. (Mol Cell Biochem 261: 117–122, 2004)

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hahn WC, Weinberg RA: Modelling the molecular circuitry of cancer. Nat Rev Cancer 2: 331–341, 2002

    Article  CAS  PubMed  Google Scholar 

  2. Howlett AR, Bissell MJ: The influence of tissue microenvironment (stroma and extracellular matrix) on the development and function of mammary epithelium. Epithelial Cell Biol 2: 79–89, 1993

    CAS  PubMed  Google Scholar 

  3. Schurch W, Seemayer TA, Lagace R: Stromal myofibroblasts in primary invasive and metastatic carcinomas. A combined immunological, light and electron microscopic study. Virchows Arch A Pathol Anat Histopathol 391: 125–139, 1981

    CAS  Google Scholar 

  4. Mahfouz SM, Chevallier M, Grimaud JA: Distribution of the major connective matrix components of the stromal reaction in breast carcinoma. An immunohistochemical study. Cell Mol Biol 33: 453–467, 1987

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  6. Ronnov-Jessen L, Petersen OW, Bissell MJ: Cellular changes involved in conversion of normal to malignant breast: Importance of the stromal reaction. Physiol Rev 76: 69–125, 1996

    CAS  PubMed  Google Scholar 

  7. Elenbaas B, Weinberg RA: Heterotypic signaling between epithelial tumour cells and fibroblasts in carcinoma formation. Exp Cell Res 264: 169–184, 2001

    Article  CAS  PubMed  Google Scholar 

  8. Sappino AP, Schurch W, Gabbiani G: Differentiation repertoire of fibroblastic cells: Expression of cytoskeletal proteins as marker of phenotypic modulations. Lab Invest 63: 144–161, 1990

    CAS  PubMed  Google Scholar 

  9. Tlsty TD, Hein PW: Know thy neighbor: Stromal cells can contribute oncogenic signals. Curr Opin Genet Dev. 11: 54–59, 2001

    Article  CAS  PubMed  Google Scholar 

  10. Hooff van den A: Stromal involvement in malignant growth. Adv Cancer Res 50: 159–196, 1988

    Google Scholar 

  11. Atherton AJ, Monaghan P, Warburton MJ, Robertson D, Kenny AJ, Gusterson BA: Dipeptidyl peptidase IV expression identifies a functional sub-population of breast fibroblasts. Int J Cancer 50: 15–19, 1992

    CAS  PubMed  Google Scholar 

  12. Garin-Chesa P, Old LJ, Rettig WJ: Cell surface glycoprotein of reactive stromal fibroblasts as a potential antibody target in human epithelial cancers. Proc Natl Acad Sci U S A 87: 7235–7239, 1990

    CAS  PubMed  Google Scholar 

  13. Nakamura T, Matsumoto K, Kiritoshi A, Tano Y, Nakamura T: Induction of hepatocyte growth factor in fibroblasts by tumour-derived factors affects invasive growth of tumour cells: In vitro analysis of tumour-stromal interactions. Cancer Res 57: 3305–3313, 1997

    CAS  PubMed  Google Scholar 

  14. Rasmussen AA, Cullen KJ: Paracrine/autocrine regulation of breast cancer by the insulin-like growth factors. Breast Cancer Res Treat 47: 219–233, 1998

    Article  CAS  PubMed  Google Scholar 

  15. Basset P, Bellocq JP, Wolf C, Stoll I, Hutin P, Limacher JM, Podhajcer OL, Chenard MP, Rio MC, Chambon P: A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature 348: 699–704, 1990

    Article  CAS  PubMed  Google Scholar 

  16. Kurose K, Gilley K, Matsumoto S, Watson PH, Zhou XP, Eng C: Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas. Nat Genet 32: 355–357, 2002

    Article  CAS  PubMed  Google Scholar 

  17. McLaughlin ME, Jacks T: Thinking beyond the tumour cell: Nf1 haploinsufficiency in the tumour environment. Cancer Cell 1: 408–410, 2002

    Article  CAS  PubMed  Google Scholar 

  18. Zhu Y, Ghosh P, Charnay P, Burns DK, Parada LF: Neurofibromas in NF1: Schwann cell origin and role of tumour environment. Science 296: 920–922, 2002

    CAS  PubMed  Google Scholar 

  19. Schor SL, Schor AM, Rushton G: Fibroblasts from cancer patients display a mixture of both foetal and adult-like phenotypic characteristics. J Cell Sci 90: 401–407, 1988

    PubMed  Google Scholar 

  20. Schor SL, Haggie JA, Durning P, Howell A, Smith L, Sellwood RA, Crowther D: Occurrence of a fetal fibroblast phenotype in familial breast cancer. Int J Cancer 37: 831–836, 1986

    CAS  PubMed  Google Scholar 

  21. Camps JL, Chang SM, Hsu TC, Freeman MR, Hong SJ, Zhau HE, von Eschenbach AC, Chung LW: Fibroblast-mediated acceleration of human epithelial tumour growth in vivo. Proc Natl Acad Sci U S A 87: 75–79, 1990

    CAS  PubMed  Google Scholar 

  22. Gleave M, Hsieh J, Gao C, von Eschenbach A, Chung L: Acceleration of human prostate cancer growth in vivo by factor produced by prostate and bone fibroblasts. Cancer Res 51: 3753–3761, 1991

    CAS  PubMed  Google Scholar 

  23. Atula S, Grenman R, Syrjanen S: Fibroblasts can modulate the phenotype of malignant epithelial cells in vitro. Exp Cell Res 235: 180–187, 1997

    Article  CAS  PubMed  Google Scholar 

  24. Olumi A, Grossfeld G, Hayward S, Carroll P, Tlsty T, Cunha G: Carcinoma-associated fibroblasts direct tumour progression of initiated human prostate epithelium. Cancer Res 59: 5002–5011, 1999

    CAS  PubMed  Google Scholar 

  25. Witty JP, Wright JH, Matrisian LM: Matrix metalloproteinases are expressed during ductal and alveolar mammary morphogenesis, and misregulation of stromelysin-1 in transgenic mice induces unscheduled alveolar development. Mol Biol Cell 6: 1287–1303, 1995

    CAS  PubMed  Google Scholar 

  26. Billingham R, Orr J, Woodhouse D: Transplantation of skin components during chemical carcinogenesis with 20-methylcholanthrene. Br J Cancer 5: 417–432, 1951

    CAS  PubMed  Google Scholar 

  27. Sympson CJ, Talhouk RS, Alexander CM, Chin JR, Clift SM, Bissell MJ, Werb Z: Targeted expression of stromelysin-1 in mammary gland provides evidence of a role of proteinases in branching morphogenesis and the requirement for an intact basement membrane for tissue-specific gene expression. J Cell Biol 125: 681–693, 1994

    Article  CAS  PubMed  Google Scholar 

  28. Wilson C, Heppner K, Labosky P, Hogan B, Matrisian L: Intestinal tumourigenesis is suppressed in mice lacking the metalloproteinase matrilysin. Proc Natl Acad Sci USA 94: 1402–1407, 1997

    CAS  PubMed  Google Scholar 

  29. Masson R, Lefebvre O, Noel A, Fahime M, Chemard M, Wendling C, Kebers F, LeMeur M, Dierich A, Foidart J, et al.: In vivo evidence that stromelysin-3 metalloproteinase contributes in a paracrine manner to epithelial cell malignancy. J Cell Biol 140: 1535–1541, 1998

    Article  CAS  PubMed  Google Scholar 

  30. Rowley D: What might a stromal response mean to prostate cancer progression? Cancer Metastasis Rev 17: 411–419, 2000

    Google Scholar 

  31. Moinfar F, Man YG, Arnould L, Bratthauer GL, Ratschek M, Tavassoli FA: Concurrent and independent genetic alterations in the stromal and epithelial cells of mammary carcinoma: Implications for tumourigenesis. Cancer Res 60: 2562–2566, 2000

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Biological Chemistry, Medical School, University of Athens, 115 27, Athens, Greece

    H. Kiaris, Ch. Kalofoutis, Ch. Piperi & A. Kalofoutis

  2. Departments of Pathology, Medical School, University of Athens, 115 27, Athens, Greece

    I. Chatzistamou

  3. Departments of Cytopathology, Medical School, University of Athens, 115 27, Athens, Greece

    H. Koutselini

Authors
  1. H. Kiaris
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. Chatzistamou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ch. Kalofoutis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Koutselini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ch. Piperi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Kalofoutis
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kiaris, H., Chatzistamou, I., Kalofoutis, C. et al. Tumour–stroma interactions in carcinogenesis: Basic aspects and perspectives. Mol Cell Biochem 261, 117–122 (2004). https://doi.org/10.1023/B:MCBI.0000028746.54447.6c

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:MCBI.0000028746.54447.6c

Search

Navigation