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Fibroblast subpopulations as accelerators of tumor progression: The role of migration stimulating factor

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Epithelial-Mesenchymal Interactions in Cancer

Part of the book series: Experientia Supplementum ((EXS,volume 74))

Summary

Tumor progression is a relatively indolent process, with many years commonly intervening between the inception of an initiating genetic lesion and the development of overt malignant disease. We suggest that the perturbation of normal epithelial-mesenchymal interactions caused by the inappropriate presence of fibroblast subpopulations displaying various ‘fetal-like’ phenotypic characteristics may significantly alter the kinetics of tumor progression and hence enhance susceptibility to cancer development. In this communication, we review our own data indicating the presence of fetal-like fibroblasts in cancer patients and put these observations in the context of similar published reports. We then discuss our interpretation of these findings, emphasising the possible direct involvement of fetal-like fibroblasts in cancer pathogenesis and putting forward an epigenetic ‘clonal modulation’ model to account for their presence in cancer patients.

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References

  • Azzarone, B., Marell, M., Billard, C., Scemana, P., Chaponnier, C. and Marciera-Coelho, M. (1984) Abnormal properties of skin fibroblasts from patients with breast cancer. Int. J. Cancer 33: 759–764.

    Article  PubMed  CAS  Google Scholar 

  • Bartal, A.H., Lichtig, C., Cardo, C.C., Feit, C., Robinson, E. and Hirshaut, Y. (1986) Monoclonal antibody defining fibroblasts appearing in fetal and neoplastic tissue. J. Natl. Cancer Inst. 76: 415–419.

    PubMed  CAS  Google Scholar 

  • Basset, P., Bellocq, J.P., Wolf, C., Stoll, I., Hutin, P., Limacher, J.M., Podhajcer, O.L., Chenard, M.P., Rio, M.C. and Chambon, P. (1990) A novel metalloproteinase gene specifically expresed in stromal cells of breast carcinomas. Nature 348: 699–704.

    Article  PubMed  CAS  Google Scholar 

  • Bayreuther, K., Rodemann, H.P., Hommel, R., Dittman, K., Albiez, M. and Francz, P.I. (1988) Human skin fibroblasts in vitro differentiate along a terminal cell lineage. Proc. Natl. Acad. Sci. USA 85: 5112–5116.

    Article  PubMed  CAS  Google Scholar 

  • Birchmeier, W., Behrens, J., Weidner, K.M., Frixen, U.H. and Schipper, J. (1991) Dominant and recessive genes involved in tumor cell invasion. Curr. Opin. Cell Biol. 3: 832–840.

    Article  PubMed  CAS  Google Scholar 

  • Camps, J.L., Chang, S.M., Hsu, T.C., Freeman, M.R., Hong, S.J., Zhau, H.E., von Eschenbach, A.C. and Chung, L.W. (1990) Fibroblast-mediated acceleration of human epithelial tumor-growth in vitro. Proc. Natl. Acad. Sci USA 87: 75–79.

    Article  PubMed  CAS  Google Scholar 

  • Chen, J., Grant, M.E., Schor, A.M. and Schor, S.L. (1989) Differences between adult and foetal fibroblasts in the regulation of hyaluronate synthesis: correlation with migratory activity. J. Cell Sci. 94: 577–589.

    PubMed  CAS  Google Scholar 

  • Chiquet-Ehrismann, R., Mackie, E.J., Pearson, C.A. and Sakaura, T. (1986) Tenascin: an extracellular matrix protein involved in tissue interactions during fetal development and oncogenesis. Cell 47: 131–139.

    Article  PubMed  CAS  Google Scholar 

  • Cornil, I., Theodorescu, D., Man, S., Herlyn, M., Jambrosic, J. and Kerbel, R. S. (1991) Fibroblast cell interactions with human melanoma cells affect tumor cell growth as a function of tumor progression. Proc. Natl. Acad. Sci. USA 88: 6028–6032.

    Article  PubMed  CAS  Google Scholar 

  • Crissman, J.D., Sakr, W.A., Hussein, M.E. and Pontes, J.E. (1993) DNA quantification of intraepithelial neoplasia and invasive carcinoma of the prostate. Prostate 22: 155–162.

    Article  PubMed  CAS  Google Scholar 

  • Cullen, K.J., Smith, H.S., Hill, S., Rosen, N. and Lippman, M.E. (1991) Growth factor messenger RNA expression by human fibroblasts from benign and malignant lesions. Cancer Res. 51: 4978–4985.

    PubMed  CAS  Google Scholar 

  • Cunha, G.R., Bigsby, R.M., Cooke, P.S. and Sugimara, Y. (1985) Stromal-epithelial interactions in adult organs. Cell Diff. 17: 137–148.

    Article  CAS  Google Scholar 

  • Dabbous, M.K., Haney, L., Carter, L.M., Paul, A.K. and Reger, J. (1987) Heterogeneity of fibroblast response in host-tumor cell-cell interactions in metastatic tumors. J. Cell. Biochem. 35: 333–344.

    Article  PubMed  CAS  Google Scholar 

  • Danes, B.S., De Angeles, P., Traganos, F., Ringborg, U., Nielsen, L.H. and Melamed, M.R. (1990) Comparison of anatomical location of squamous cell carcinoma within the oral cavity and oropharynx with the incidence of in vitro hyperdiploidly. Clin. Genet. 37: 188–193.

    Article  PubMed  CAS  Google Scholar 

  • Docherty, R., Forrester, J.V., Lackie, J.M. and Gregory, D.W. (1989) Glycosaminoglycans facilitate the movement of fibroblasts through 3D collagen matrices. J. Cell Sci. 92: 263–267.

    PubMed  CAS  Google Scholar 

  • Durning, P., Schor, S.L. and Sellwood, R.A.S. (1984) Fibroblasts from patients with breast cancer show abnormal migratory behavior in vitro. Lancet ii: 890–892.

    Article  Google Scholar 

  • Dvorak, H.F. (1986) Tumors: wounds that do not heal. New Eng. J. Med. 315: 1650–1659.

    Article  PubMed  CAS  Google Scholar 

  • Edward, M., Grant, A.W. and Mackie, R.M. (1992) Human melanoma cell-derived factor(s) stimulate fibroblast glycosaminoglycan synthesis. Int. J. Cancer 52: 499–503.

    Article  PubMed  CAS  Google Scholar 

  • Ellis, I., Grey, A.M., Schor, A.M. and Schor, S.L. (1992) Antagonistic effects of transforming growth factor beta and MSF on fibroblast migration and hyaluronic acid synthesis: possible implications for dermal wound healing. J. Cell. Sci. 102: 447–456.

    PubMed  CAS  Google Scholar 

  • Elstad, C.A. and Hosick, H.L. (1987) Contribution of the extracellular matrix to the growth properties of cells from a preneoplastic outgrowth: possible role of hyaluronic acid. Exp. Cell Res. 55: 313–321.

    CAS  Google Scholar 

  • Fabra, A., Nakajima, M., Bucana, C.D. and Fidler, I.J. (1992) Modulation of the invasive phenotype of human colon carcinoma cells by organ specific fibroblasts of nude mice. Differentiation 52: 101–110.

    Article  PubMed  CAS  Google Scholar 

  • Feinberg, R.N. and Beebe, D.C. (1983) Hyaluronate in vasculogenesis. Science 220: 1177–1179.

    Article  PubMed  CAS  Google Scholar 

  • Foulds, L. (1975) Neoplastic Development, Vol. 2. Academic Press, London.

    Google Scholar 

  • Garin-Chesa, P., Old., L.J. and Retting, W.J. (1990) Cell surface glycoprotein of reactive stromal fibroblasts as a potential target in human epithelial cancers. Proc. Natl. Acad. Sci. USA 87: 7235–7239.

    Article  PubMed  CAS  Google Scholar 

  • Gärtner, M.F.R.M., Wilson, E.L. and Dowdle, E.B. (1992) Fibroblast-dependent tumori-genicity of melanoma xenografts in athymic mice. Int. J. Cancer 51: 788–791.

    Article  PubMed  Google Scholar 

  • Gleave, M., Hsieh, J.-T., Gao, C., von Eschenbach, A.C. and Chung, W.K. (1991) Acceleration of human prostate cancer growth in vivo by factors produced by prostate and bone fibroblasts. Cancer Res. 51: 3573–3761.

    Google Scholar 

  • Grey, A.M., Schor, A.M., Rushton, G., Ellis, I. and Schor, S.L. (1989) Purification of the migration stimulating factor produced by fetal and breast cancer patient fibroblasts. Proc. Natl. Acad. Sci. USA 86: 2438–2442.

    Article  PubMed  CAS  Google Scholar 

  • Haggie, J., Schor, S.L., Howell, A., Birch, J.M. and Sellwood, R.A.S. (1987) Fibroblasts from relatives of hereditary breast cancer display foetal-like behaviour in vitro. Lancet i: 1455–1457.

    Article  Google Scholar 

  • Hay, E. (1993) Extracellular matrix alters epithelial differentiation. Curr. Op. Cell Biol. 5: 1029–1035.

    Article  PubMed  CAS  Google Scholar 

  • Helin, K. and Harlow, E. (1993) The retinoblastoma protein as a transcriptional repressor. Trends Cell Biol. 3: 43–46.

    Article  PubMed  CAS  Google Scholar 

  • Irwin, C.R., Picardo, M., Ellis, I., Sloan, P., Grey, A.M., McGurk, M. and Schor, S.L. (1994) Inter-and intrasite heterogeneity in the expression of fetal-like phenotypic characteristics by gingival fibroblasts: potential significance for wound healing. J. Cell Sci. 107: 1333–1346.

    PubMed  Google Scholar 

  • Knudson, A.G. (1977) Genetics and etiology of human cancer. Adv. Hum. Genet. 8: 1–66.

    PubMed  CAS  Google Scholar 

  • Knudson, W., Biswas, C., Li, X.-Q., Nemec, R.E. and Toole, B.P. (1989) The role and regulation of tumor-associated hyaluronanh. In: The Biology of Hyaluronan. Ciba Foundation Symposium 143. John Wiley and Sons, Chichester, pp 150–159.

    Google Scholar 

  • Lu, C., Vickers, M.F. and Kerbel, R.S. (1992) Interleukin 6: a fibroblast-derived growth inhibitor of human melanoma cells from early but not advanced stages of tumor progression. Proc. Natl. Acad. Sic. USA 89: 9215–9219.

    Article  CAS  Google Scholar 

  • Lynch, H.T., Albano, W.A., Heieck, J.J., Mulcahy, G.M., Lynch, J.F., Layton, M.A. and Danes, B.S. (1984) Genetics, biomarkers and control of breast cancer: a review. Cancer Genet. Cytogenet. 13: 43–92.

    Article  PubMed  CAS  Google Scholar 

  • Markwald, R.R., Fitzharris, T.P., Bank, H. and Bernanke, D.H. (1978) Structural analysis on the material organization of glycosaminoglycans in developing endocardial cushions. Dev. Biol. 62: 292–316.

    Article  PubMed  CAS  Google Scholar 

  • Matsumoto, K., Horikoshi, M., Rikimaru, K. and Enomoto, S. (1989) A study of an in vitro model of squamous cell carcinoma. J. Oral. Pathol. Med. 18: 498–501.

    Article  PubMed  CAS  Google Scholar 

  • McNeal, J.E. (1984) Anatomy of the prostate and morphogenesis of BPH: In: A.B. Kimbal, K. Buhl and H.C. Carter (eds): New Approaches to the Study of Benign Prostatic Hyperplasia. A.R. Liss, Inc., New York, pp 27–53.

    Google Scholar 

  • Mintz, B. and Illmensee, K. (1975) Normal genetically mosaic mice produced from malignant teratorcarcinoma cells. Proc. Natl. Acad. Sci. USA 72: 3585–3589.

    Article  PubMed  CAS  Google Scholar 

  • Mukaida, H., Hirabayashi, N., Hirai, T., Iwata, T., Saeki, S. and Toge, T. (1991) Significance of freshly cultured fibroblasts from different tissues in promoting cancer cell growth. Int. J. Cancer 48: 423–427.

    Article  PubMed  CAS  Google Scholar 

  • Nakajima, M. and Chop, A. (1991) Tumor invasion and extracellular marix degradative enzymes: regulation of activity of organ factors. Seminars Cancer Biol. 2: 115–127.

    CAS  Google Scholar 

  • Nakano, S. and Ts’O, P.O. (1981) Cellular differentiation and neoplasia: characterization of subpopulations of cells that have neoplasia related growth properties in Syrian hamster embryo cell cultures. Proc. Natl. Acad. Sci. USA 78: 4995–4999.

    Article  PubMed  CAS  Google Scholar 

  • Nathan, C. and Sporn, M. (1991) Cytokines in context. J. Cell Biol. 113: 981–986.

    Article  PubMed  CAS  Google Scholar 

  • Neugut, A.I., Sherr, D., Robinson, E., Murray, T. and Nieves, J. (1992) Differences between first and second primary lung cancer. Cancer Epidemiol. Biomarkers 1: 109–112.

    CAS  Google Scholar 

  • Nielsen, M., Thomsen, J.L., Primdahl, S., Dyreborg, U. and Andersen, J.A. (1987) Breast flcancer and atypia among young and middle-aged women. Br. J. Cancer 56: 814–881.9.

    Article  PubMed  CAS  Google Scholar 

  • Nicolo, G., Salvi, S., Oliveri, G., Borsi, L., Castellani, P. and Zardi, L. (1990) Expression of tenascin and the ED-B containing oncofetal fibronectin isoform in human cancer. Cell. Differ. Dev. 32: 401–408.

    Article  PubMed  CAS  Google Scholar 

  • Nohammer, G., Bajardi, F., Benedetto, C., Kresbach, H., Rojanapo, W. and Schauenstein, E. (1989) Histophotometric quantification of the field effect and the extended field effect of tumors. Free Rad. Res. Commun. 7: 129–137.

    Article  CAS  Google Scholar 

  • Ogden, G.R., Lane, E.B., Hopwood, D.V. and Chisholm, D.M. (1993) Evidence for field change in oral cancer based on cytokeratin expression. Br. J. Cancer 67: 1324–1330.

    Article  PubMed  CAS  Google Scholar 

  • Ottman, R., King, M.C., Pike, M.C. and Henderson, B.E. (1983) Practical guide for estimating risk for familial breast cancer. Lancet ii: 556–558.

    Article  Google Scholar 

  • Picard, O., Rolland, Y. and Poupon, M.F. (1986) Fibroblast-dependent tumorigenicity of cells in nude mice: implication for implantation and metastasis. Cancer Res. 46: 3290–3294.

    PubMed  CAS  Google Scholar 

  • Picardo, M., Schor, S.L., Grey, A.M., Howell, A., Laidlow, I., Redford, J. and Schor, A.M. (1991) Migration stimulating activity in serum of breast cancer patients. Lancet 337: 130–133.

    Article  PubMed  CAS  Google Scholar 

  • Picardo, M., Grey, A.M., McGurk, M., Ellis, I. and Schor, S.L. (1992) Identification of migration stimulating factor in wound fluid. Exp. Mol. Path. 57: 8–21.

    Article  CAS  Google Scholar 

  • Pitot, H.C. and Cambell, H.A. (1987) An approach to the determination of the relative potencies of chemical agents during the stages of initiation and promotion in multistage hepatocarcinogenesis in the rat. Environ. Health Perspect. 76: 49–56.

    Article  PubMed  CAS  Google Scholar 

  • Rosen, E.M. and Goldberg, I.D. (1989) Protein factors which regulate cell motility. In Vitro 25: 1079–1087.

    CAS  Google Scholar 

  • Rubin, H. (1985) Cancer as a dynamic developmental disorder. Cancer Res. 45: 2935–2942.

    PubMed  CAS  Google Scholar 

  • Sappino, A.P., Schurch, W. and Gabbiani, G. (1990) Differentiation repertoire of fibroblastic cells: expression of cytoskeletal proteins as marker of phenotypic modulations. Lab. Invest. 63: 144–161.

    PubMed  CAS  Google Scholar 

  • Schor, S.L. (1980) Cell proliferation and migration within three-dimensional collagen gels. J. Cell Sci. 41: 159–175.

    PubMed  CAS  Google Scholar 

  • Schor, S.L., Schor, A.M., Durning, P. and Rushton, G. (1985a) Skin fibroblasts obtained from cancer patients display foetal-like migratory behaviour on collagen gels. J. Cell Sci. 73: 235–244.

    PubMed  CAS  Google Scholar 

  • Schor, S.L., Schor, A.M., Rushton, G. and Smith, L. (1985b) Adult, foetal, and transformed fibroblasts display different migratory phenotypes on collagen gels: Evidence for an isoformic transition during foetal development. J. Cell Sci. 73: 221–234.

    PubMed  CAS  Google Scholar 

  • Schor, S.L., Haggie, J., Durning, P., Howell, A., Sellwood, R.A.S. and Crowther, D. (1986) The occurrence of a foetal fibroblast phenotype in breast cancer. Int. J. Cancer 37: 831–836.

    Article  PubMed  CAS  Google Scholar 

  • Schor, S.L. and Schor, A.M. (1987) Clonal heterogeneity in fibroblasts: implications for the control of epithelial-mesenchymal interactions. BioEssays 7: 200–204.

    Article  PubMed  CAS  Google Scholar 

  • Schor, S.L., Schor, A.M., Howell, A. and Crowther, D. (1987) Hypothesis: persistent expression of fetal phenotypic characteristics by fibroblasts is associated with an increased susceptibility to neoplastic disease. Exp. Cell Biol. 55: 11–17.

    PubMed  CAS  Google Scholar 

  • Schor, S.L., Schor, A.M. and Rushton, G. (1988a) Fibroblasts from cancer patients display a mixture of both foetal and adult-like phenotypic characteristics. J. Cell Sci. 90: 401–407.

    PubMed  Google Scholar 

  • Schor, S.L., Schor, A.M., Grey, A.M. and Rushton, G. (1988b) Fetal and cancer patient fibroblasts produce an autocrine migration stimulating factor not made by normal adult cells. J. Cell Sci. 90: 391–399.

    PubMed  CAS  Google Scholar 

  • Schor, S.L., Schor, A.M., Grey, A.M., Chen, J., Rushton, G. and Ellis, I. (1989) Mechanism of action of the migration stimulating factor produced by fetal and cancer patient fibroblasts: effect on hyaluronic acid synthesis. In Vitro 25: 737–746.

    CAS  Google Scholar 

  • Schor, S.L., Grey, A.M., Ellis, I., Schor, A.M., Coles, B. and Murphy, R. (1993) Migration stimulating factor: its structural homology to the gelatin-binding domain of fibronectin, mode of action and possible function in health and disease. In: G. Evans, C. Wigley and R. Warn (eds): Cell Behaviour: Adhesion and Motility. S.E.B. Symposium, No. 47, pp. 235–251.

    Google Scholar 

  • Schor, S.L. (1994) Cytokine control of cell motility: modulation and mediation by the extracellular matrix. Prog. Growth Factor Res. 5: 223–248.

    Article  PubMed  CAS  Google Scholar 

  • Schor, A.M., Rushton, G., Ferguson, J.E., Howell, A., Redford, J. and Schor, S.L. (1994) Phenotypic heterogeneity in breast fibroblasts: functional anomaly in fibroblasts from histologically normal tissue adjacent to carcinoma. Int. J. Cancer. 59: 25–32.

    Article  PubMed  CAS  Google Scholar 

  • Slaughter, D.P., Southwick, H.W. and Smejkal, W. (1953) Field cancerization in oral stratified squamous epithelium. Cancer 6: 963–968.

    Article  PubMed  CAS  Google Scholar 

  • Sloan, P., Schor, S.L. and Lopes, V. (1990) Immunohistochemical study of the heterogeneity of tenascin distribution within the oral mucosa of the mouse. Archs. oral Biol. 35: 67–70.

    Article  CAS  Google Scholar 

  • Steeg, P. (1991) Genetic control of the metastatic phenotype. Seminars Cancer Cell Biol. 2: 105–110.

    CAS  Google Scholar 

  • Stoker, A.W., Hatier, C. and Bissell, M.J. (1990) The embryonic environment strongly attenuates v-src oncogenesis in mesenchymal and epithelial tissues, but not in endothelia. J. Cell Biol. 111: 217–228.

    Article  PubMed  CAS  Google Scholar 

  • Svendsen, L.B., Thorup, J., Larson, J.K., Norgard, T., Willumsen, H. and Hansen, O.H. (1989) Association between tumor DNA aneuploidy and in vitro tetraploidy of skin fibroblasts in patients with colorectal neoplasms. Scand. J. Gastroenterol. 24: 755–760.

    Article  PubMed  CAS  Google Scholar 

  • Tanaka, H., Mori, Y., Ishii, H. and Akedo, H. (1988) Enhancement of metastatic capacity of fibroblast-tumor cell interaction in mice. Cancer Res. 48: 1456–1459.

    PubMed  CAS  Google Scholar 

  • Thielmann, H.W., Edler, L., Burkhardt, M.R. and Jung, E.G. (1987) DNA repair synthesis in fibroblast strains from patients with actinic keratosis, squamous cell carcinoma, basal cell carcinoma, or malignant melanoma after treatment with ultraviolet light, N-acetoxy-2-acetyl-aminofluorene, methyl methanesulfonate and N-methyl-N-nitrosurea. J. Cancer Res. Clin. Oncol. 113: 171–186.

    Article  PubMed  CAS  Google Scholar 

  • Toole, B.P. and Trelstad, R.L. (1971) Hyaluronate production and removal during corneal development in the chick. Dev. Biol. 26: 28–35.

    Article  PubMed  CAS  Google Scholar 

  • Toole, B.P., Biswas, C. and Gross, J. (1979) Hyaluronate and invasiveness of the rabbit V2 carcinoma. Proc. Natl. Acad. Sci. USA 76: 6299–6303.

    Article  PubMed  CAS  Google Scholar 

  • Turley, E.A. and Torrance, J. (1984) Localization of hyaluronate and hyaluronate-binding protein on motile and non-motile fibroblasts. Expl. Cell Res. 161: 17–28.

    Article  Google Scholar 

  • Wynford-Thomas, D., Smith, P. and Williams, E.D. (1986) Prolongation of fibroblast lifespan associated with epithelial rat tumor development. Cancer Res. 46: 3125–3127.

    PubMed  CAS  Google Scholar 

  • Zetter, B.R. and Brightman, S.E. (1990) Cell motility and the extracellular matrix. Curr. Opin. Cell Biol. 2: 850–856.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Dental Surgery and Periodontology, The Dental School, University of Dundee, Dundee, DD1 4HR, Scotland, UK

    S. L. Schor

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  1. S. L. Schor
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  1. Institute of Oncology, Long Island Jewish Medical Center, New Hyde Park, N.Y., 11042, USA

    I. D. Goldberg  & E. M. Rosen  & 

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Schor, S.L. (1995). Fibroblast subpopulations as accelerators of tumor progression: The role of migration stimulating factor. In: Goldberg, I.D., Rosen, E.M. (eds) Epithelial-Mesenchymal Interactions in Cancer. Experientia Supplementum, vol 74. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-9070-0_14

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  • DOI: https://doi.org/10.1007/978-3-0348-9070-0_14

  • Publisher Name: Birkhäuser Basel

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