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. 1993 Nov;68(5):909–915. doi: 10.1038/bjc.1993.453

Enhancement of tumorigenicity of human breast adenocarcinoma cells in nude mice by matrigel and fibroblasts.

A Noël 1, M C De Pauw-Gillet 1, G Purnell 1, B Nusgens 1, C M Lapiere 1, J M Foidart 1
PMCID: PMC1968733  PMID: 8217606

Abstract

The failure of MCF7 cells to induce the formation of tumours after sub-cutaneous inoculation into athymic nude mice can be obviated by the simultaneous injection of an extract of basement membrane proteins (matrigel). Tumour growth is promoted and the latency period is low (2 to 4 weeks). In the absence of matrigel, the simultaneous inoculation of fibroblasts and MCF7 cells also resulted in the development of tumours, but with a longer latency period (about 2 months). The tumorigenic synergy between matrigel and fibroblasts was evidenced by co-inoculating MCF7 cells MDA-MB 231 cells with fibroblasts and matrigel. This co-inoculation decreased the delay of appearance of the tumours and/or accelerated the tumour growth, depending upon the number of fibroblasts injected. Repeated injections of fibroblasts conditioned medium, at the site of inoculum of tumour cells also enhanced tumour growth, suggesting the involvement of soluble factors secreted by fibroblasts. Histologically, tumours induced by co-inoculation of tumour cells and fibroblasts contained more stromal structures including vimentin-positive cells, fibronectin and interstitial collagens. These data suggest that human tumours may be reconstituted and grown in athymic nude mice using basement membrane components and fibroblasts as inductors.

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Selected References

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  1. Attia M. A., Weiss D. W. Immunology of spontaneous mammary carcinomas in mice. V. Acquired tumor resistance and enhancement in strain A mice infected with mammary tumor virus. Cancer Res. 1966 Aug;26(8):1787–1800. [PubMed] [Google Scholar]
  2. Bashkin P., Doctrow S., Klagsbrun M., Svahn C. M., Folkman J., Vlodavsky I. Basic fibroblast growth factor binds to subendothelial extracellular matrix and is released by heparitinase and heparin-like molecules. Biochemistry. 1989 Feb 21;28(4):1737–1743. doi: 10.1021/bi00430a047. [DOI] [PubMed] [Google Scholar]
  3. Bell E., Ivarsson B., Merrill C. Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1274–1278. doi: 10.1073/pnas.76.3.1274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cailleau R., Young R., Olivé M., Reeves W. J., Jr Breast tumor cell lines from pleural effusions. J Natl Cancer Inst. 1974 Sep;53(3):661–674. doi: 10.1093/jnci/53.3.661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Camps J. L., Chang S. M., Hsu T. C., Freeman M. R., Hong S. J., Zhau H. E., von Eschenbach A. C., Chung L. W. Fibroblast-mediated acceleration of human epithelial tumor growth in vivo. Proc Natl Acad Sci U S A. 1990 Jan;87(1):75–79. doi: 10.1073/pnas.87.1.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Clemmons D. R. Multiple hormones stimulate the production of somatomedin by cultured human fibroblasts. J Clin Endocrinol Metab. 1984 May;58(5):850–856. doi: 10.1210/jcem-58-5-850. [DOI] [PubMed] [Google Scholar]
  7. Coucke P., De Leval L., Leyh P., Bonjean K., Siwek B., Noel A., De Pauw-Gillet M. C., Paulus J. M., Bassleer R., Foidart J. M. Influence of laminin or fibroblasts upon colony formation in the mouse by B16 melanoma cell spheroids: a morphometric analysis. In Vivo. 1992 Mar-Apr;6(2):119–124. [PubMed] [Google Scholar]
  8. Emonard H., Calle A., Grimaud J. A., Peyrol S., Castronovo V., Noel A., Lapière C. M., Kleinman H. K., Foidart J. M. Interactions between fibroblasts and a reconstituted basement membrane matrix. J Invest Dermatol. 1987 Aug;89(2):156–163. doi: 10.1111/1523-1747.ep12470552. [DOI] [PubMed] [Google Scholar]
  9. Esterre P., Melin M., Serrar M., Grimaud J. A. New specific markers of human and mouse fibroblasts. Cell Mol Biol. 1992 May;38(3):297–301. [PubMed] [Google Scholar]
  10. Fridman R., Giaccone G., Kanemoto T., Martin G. R., Gazdar A. F., Mulshine J. L. Reconstituted basement membrane (matrigel) and laminin can enhance the tumorigenicity and the drug resistance of small cell lung cancer cell lines. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6698–6702. doi: 10.1073/pnas.87.17.6698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fridman R., Kibbey M. C., Royce L. S., Zain M., Sweeney M., Jicha D. L., Yannelli J. R., Martin G. R., Kleinman H. K. Enhanced tumor growth of both primary and established human and murine tumor cells in athymic mice after coinjection with Matrigel. J Natl Cancer Inst. 1991 Jun 5;83(11):769–774. doi: 10.1093/jnci/83.11.769. [DOI] [PubMed] [Google Scholar]
  12. Gärtner M. F., Wilson E. L., Dowdle E. B. Fibroblast-dependent tumorigenicity of melanoma xenografts in athymic mice. Int J Cancer. 1992 Jul 9;51(5):788–791. doi: 10.1002/ijc.2910510520. [DOI] [PubMed] [Google Scholar]
  13. Horgan K., Jones D. L., Mansel R. E. Mitogenicity of human fibroblasts in vivo for human breast cancer cells. Br J Surg. 1987 Mar;74(3):227–229. doi: 10.1002/bjs.1800740326. [DOI] [PubMed] [Google Scholar]
  14. Kleinman H. K., McGarvey M. L., Hassell J. R., Star V. L., Cannon F. B., Laurie G. W., Martin G. R. Basement membrane complexes with biological activity. Biochemistry. 1986 Jan 28;25(2):312–318. doi: 10.1021/bi00350a005. [DOI] [PubMed] [Google Scholar]
  15. Liotta L. A. Tumor invasion and metastases: role of the basement membrane. Warner-Lambert Parke-Davis Award lecture. Am J Pathol. 1984 Dec;117(3):339–348. [PMC free article] [PubMed] [Google Scholar]
  16. Miller F. R., McInerney D. Epithelial component of host-tumor interactions in the orthotopic site preference of a mouse mammary tumor. Cancer Res. 1988 Jul 1;48(13):3698–3701. [PubMed] [Google Scholar]
  17. Nathan C., Sporn M. Cytokines in context. J Cell Biol. 1991 Jun;113(5):981–986. doi: 10.1083/jcb.113.5.981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Noel A., Callé A., Emonard H., Nusgens B., Foidart J. M., Lapiere C. M. Antagonistic effects of laminin and fibronectin in cell-to-cell and cell-to-matrix interactions in MCF-7 cultures. In Vitro Cell Dev Biol. 1988 May;24(5):373–380. doi: 10.1007/BF02628488. [DOI] [PubMed] [Google Scholar]
  19. Noel A., Munaut C., Boulvain A., Calberg-Bacq C. M., Lambert C. A., Nusgens B., Lapiere C. M., Foidart J. M. Modulation of collagen and fibronectin synthesis in fibroblasts by normal and malignant cells. J Cell Biochem. 1992 Feb;48(2):150–161. doi: 10.1002/jcb.240480207. [DOI] [PubMed] [Google Scholar]
  20. Noel A., Munaut C., Nusgens B., Foidart J. M., Lapiere C. M. The stimulation of fibroblasts' collagen synthesis by neoplastic cells is modulated by the extracellular matrix. Matrix. 1992 Jun;12(3):213–220. doi: 10.1016/s0934-8832(11)80064-8. [DOI] [PubMed] [Google Scholar]
  21. Noel A., Simon N., Raus J., Foidart J. M. Basement membrane components (matrigel) promote the tumorigenicity of human breast adenocarcinoma MCF7 cells and provide an in vivo model to assess the responsiveness of cells to estrogen. Biochem Pharmacol. 1992 Mar 17;43(6):1263–1267. doi: 10.1016/0006-2952(92)90501-9. [DOI] [PubMed] [Google Scholar]
  22. Noël A. C., Callé A., Emonard H. P., Nusgens B. V., Simar L., Foidart J., Lapiere C. M., Foidart J. M. Invasion of reconstituted basement membrane matrix is not correlated to the malignant metastatic cell phenotype. Cancer Res. 1991 Jan 1;51(1):405–414. [PubMed] [Google Scholar]
  23. Picard O., Rolland Y., Poupon M. F. Fibroblast-dependent tumorigenicity of cells in nude mice: implication for implantation of metastases. Cancer Res. 1986 Jul;46(7):3290–3294. [PubMed] [Google Scholar]
  24. Pretlow T. G., Delmoro C. M., Dilley G. G., Spadafora C. G., Pretlow T. P. Transplantation of human prostatic carcinoma into nude mice in Matrigel. Cancer Res. 1991 Jul 15;51(14):3814–3817. [PubMed] [Google Scholar]
  25. Price J. E., Zhang R. D. Studies of human breast cancer metastasis using nude mice. Cancer Metastasis Rev. 1990 Feb;8(4):285–297. doi: 10.1007/BF00052605. [DOI] [PubMed] [Google Scholar]
  26. Robinson S. P., Jordan V. C. Antiestrogenic action of toremifene on hormone-dependent, -independent, and heterogeneous breast tumor growth in the athymic mouse. Cancer Res. 1989 Apr 1;49(7):1758–1762. [PubMed] [Google Scholar]
  27. Soule H. D., Vazguez J., Long A., Albert S., Brennan M. A human cell line from a pleural effusion derived from a breast carcinoma. J Natl Cancer Inst. 1973 Nov;51(5):1409–1416. doi: 10.1093/jnci/51.5.1409. [DOI] [PubMed] [Google Scholar]
  28. Stoker M., Gherardi E. Regulation of cell movement: the motogenic cytokines. Biochim Biophys Acta. 1991 Apr 16;1072(1):81–102. doi: 10.1016/0304-419x(91)90008-9. [DOI] [PubMed] [Google Scholar]
  29. Tanaka H., Mori Y., Ishii H., Akedo H. Enhancement of metastatic capacity of fibroblast-tumor cell interaction in mice. Cancer Res. 1988 Mar 15;48(6):1456–1459. [PubMed] [Google Scholar]
  30. Taub M., Wang Y., Szczesny T. M., Kleinman H. K. Epidermal growth factor or transforming growth factor alpha is required for kidney tubulogenesis in matrigel cultures in serum-free medium. Proc Natl Acad Sci U S A. 1990 May;87(10):4002–4006. doi: 10.1073/pnas.87.10.4002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Vukicevic S., Kleinman H. K., Luyten F. P., Roberts A. B., Roche N. S., Reddi A. H. Identification of multiple active growth factors in basement membrane Matrigel suggests caution in interpretation of cellular activity related to extracellular matrix components. Exp Cell Res. 1992 Sep;202(1):1–8. doi: 10.1016/0014-4827(92)90397-q. [DOI] [PubMed] [Google Scholar]
  32. Yee D., Cullen K. J., Paik S., Perdue J. F., Hampton B., Schwartz A., Lippman M. E., Rosen N. Insulin-like growth factor II mRNA expression in human breast cancer. Cancer Res. 1988 Dec 1;48(23):6691–6696. [PubMed] [Google Scholar]
  33. van Roozendaal C. E., van Ooijen B., Klijn J. G., Claassen C., Eggermont A. M., Henzen-Logmans S. C., Foekens J. A. Stromal influences on breast cancer cell growth. Br J Cancer. 1992 Jan;65(1):77–81. doi: 10.1038/bjc.1992.14. [DOI] [PMC free article] [PubMed] [Google Scholar]

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