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In vitro degradation of extracellular matrix by human ovarian carcinoma cells

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Better in vitro models arc needed to elucidate the mechanisms underlying tissue destruction by human tumor cells. To address this matter recently isolated and characterized human ovarian carcinoma cell lines derived from either primary tumors, ascitic effusions or metastatic growths were plated in direct contact with extracellular matrix (ECM) previously deposited on culture dishes by bovine corneal endothelial cells. Light and electron microscopy of four of the five ovarian tumor cell lines demonstrated morphologic digestion with penetration of ECM by tumor cell microvilli, along with associated rarefaction. The ability of these same ovarian tumor cell lines to solubilize specific carbohydrate and protein moieties present in intact ECM was assessed with the use of metabolically prelabeled ECM employing tritiated fucose, galactose, glucosamine and proline. Results from these studies corroborated morphologic observations in which four of the five tumor cell lines tested extensively solubilized radiolabeled ECM. The kinetics of radiolabel release from ECM illustrated that three of the four invasive tumors released [3H]fucose, [3H]glucosamine and [3H]proline at high rates. Normal human ovarian fibroblasts and mesothelial cells were observed to be unable to digest ECM and this was consistent with their inability to release radiolabeled material from prelabeled ECM. The results from these studies suggest that some ovarian carcinomas have the ability to degrade basement membrane components. Knowledge regarding the mechanisms responsible for tissue degradation may eventually lead to the development of new chemotherapeutic modalities designed to restrict tumor cell invasion, growth and metastasis.

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References

  1. Barsky, S. H., Siegal, G., Jannotta, F., and Liotta, L. A., 1983, Loss of basement membrane components by invasive tumors but not by their benign counterparts. Laboratory Investigation, 49, 140–148.

    Google Scholar 

  2. Bergman, F., 1966, Carcinoma of the ovary: A clinicopathological study of 86 autoposied cases with special reference to mode of spread. Acta obstetrica et gynecologica Scandinavia, 45, 211–231.

    Google Scholar 

  3. Bernacki, R. J., Niedbala, M. J., and Korytnyk, W., 1985, Glycosidases in cancer and invasion.Cancer Metastasis Reviews, 4, 81–102.

    Google Scholar 

  4. Bernstein, P., 1936, Tumors of the ovary: A study of 1101 cases of operations for ovarian tumors. American Journal of Obstetrics and Gynecology, 32, 1023–1039.

    Google Scholar 

  5. Bogenmann, E., Mark, C., Isaacs, H., Neustein, H. B., Declerck, Y. A., Laug, W. F., and Jones, P. A., 1983, Invasive properties of primary pediatric neoplasms in vitro. Cancer Research, 43, 1176–1186.

    Google Scholar 

  6. Carr, I., Mcginty, F., and Norris, P., 1976, The fine structure of neoplastic invasion of liver skeletal muscle and lymphatic vessels by the Rd/3 tumor. Journal of Pathology, 118,91–99.

    Google Scholar 

  7. Crickard, K., Crickard, U., and Yoonessi, M., 1983, Human ovarian carcinoma cells maintained on extracellular matrix versus plastic. Cancer Research, 43, 2762–2767.

    Google Scholar 

  8. Crickard, K., Crickard, U., Yoonessi, M., and Caglar, H., 1986, Extracellular matrix-coated culture dishes: An in vitro model for primary human gynecologic tumors. Cancer Genetics and Cytogenetics, 19, 51–56.

    Google Scholar 

  9. Crickard, K., Crickard, U., Yoonessi, M., Niedbala, M. J., and Bernacki, R. J., 1986, Long-term cultures of human ovarian and endometrial cancer cells maintained on extracellular matrix. Proceedings of the American Association of Cancer Research, 27, 30.

    Google Scholar 

  10. Dingemanns, K. P., Roos, E., Van den Bergh Weerman, M. A., and Van de Pavert, I. V., 1978, Invasion of liver tissue by tumor cells and leukocytes: Comparative ultrastructure. Journal of the National Cancer Institute, 60, 583–598.

    Google Scholar 

  11. Etherington, D. L., 1977, The dissolution of insoluble bovine collagens by cathepsin B1 collagenolytic cathepsin, and pepsin: The influence of collagen type, age and chemical purity on susceptibility. Connective Tissue Research, 5, 135–145.

    Google Scholar 

  12. Feldman, G. B., 1975, Lymphatic obstruction in carcinomatous ascites. Cancer Research, 35, 325–332.

    Google Scholar 

  13. Frankfurt, O. S., 1983, Increased uptake of vital dye Hoechst 33342 during S phase in synchronized HeLa S3 cells. Cytometry, 4, 216–221.

    Google Scholar 

  14. Gospodarowicz, D., Bialecki, H., and Greenburg, G., 1978, Purification of fibroblast growth factor activity from bovine brain. Journal of Biological Chemistry, 253, 3736–3743.

    Google Scholar 

  15. Gospodarowicz, D., Greenburg, G., Foidart, J. M., and Savion, N., 1981, The production and localization of laminin in cultured vascular and corneal endothelial cells. Journal of Cellular Physiology, 107, 173–183.

    Google Scholar 

  16. Gospodarowicz, D., Mescher, A. L., and Birdwell, C. R., 1977, Stimulation of corneal endothelial cell proliferation in vitro by fibroblast and epidermal growth factors. Experimental Eye Research, 25, 75–89.

    Google Scholar 

  17. Hirabayashi, K., and Graham, J., 1970, Genesis of ascites in ovarian cancer. American Journal of Obstetrics and Gynecology, 106, 492–497.

    Google Scholar 

  18. Iozzo, R. V., 1985, Biology of disease. Proteoglycans: structure function and role in neoplasia. Laboratory Investigation, 53, 373–396.

    Google Scholar 

  19. Jones, P. A., and Declerck, Y. A., 1980, Destruction of extracellular matrices containing glycoproteins, elastin and collagen by metastatic human tumor cells. Cancer Research, 40, 3222–3227.

    Google Scholar 

  20. Jones, P. A., and Declerck, Y. A., 1982, Extracellular matrix destruction by invasive tumor cells. Cancer Metastasis Reviews, 1, 289–317.

    Google Scholar 

  21. Kramer, R. H., Vogel, K. G., and Nicolson, G. L., 1982, Solubilization and degradation of subendothelial matrix glycoproteins and proteoglycans by metastatic tumor cells. Journal of Biological Chemistry, 257, 2678–2686.

    Google Scholar 

  22. Laug, W. E., Declerck, Y. A., and Jones, P. A., 1983, Degradation of the subendothelial matrix by tumor cells. Cancer Research, 43, 1827–1834.

    Google Scholar 

  23. Liotta, L. A., Rao, C. N., and Barsky, S. H., 1983, Tumor invasion and the extracellular matrix. Laboratory Investigation, 49, 636–649.

    Google Scholar 

  24. Liotta, L. A., Thorgeirsson, U. P., and Garbisa, S., 1982, Role of collagenases in tumor cell invasion. Cancer Metastasis Reviews, 1, 277–288.

    Google Scholar 

  25. Ludatsher, R. M., Luse, S. A., and Suntzeff, V., 1967, An electron microscopic study of pulmonary tumor emboli from transplanted Morris hepatoma 5123. Cancer Research, 27, 1939–1952.

    Google Scholar 

  26. Nevo, Z., Gonzalez, R., and Gospodarowicz, D., 1984, Extracellular matrix proteoglycans produced by cultured bovine corneal endothelial cells. Connective Tissue Research, 13, 45–57.

    Google Scholar 

  27. Nicolson, G., 1982, Metastatic tumor cell attachment and invasion assay utilizing vascular endothelial cell monolayers. Journal of Histochemistry and Cytochemistry, 30, 214–220.

    Google Scholar 

  28. Niedbala, M. J., Crickard, K., and Bernacki, R. J., 1985, Interaction of human ovarian tumor cells with human mesothelial cells grown on extracellular matrix: an in vitro model system for studying tumor cell adhesion and invasion. Experimental Cell Research, 160, 499–513.

    Google Scholar 

  29. Niedbala, M. J., Crickard, K., and Bernacki, R. J., 1985, Interactions of human ovarian and endometrial carcinoma cells with extracellular matrix: An in vitro model to study tumor cell invasion. Proceedings of the American Association for Cancer Research, 26, 55.

    Google Scholar 

  30. Pauli, B. U., Schwartz, D. E., Thonar, E. J. M., and Kuettner, K. E., 1983, Tumor invasion and host extracellular matrix. Cancer Metastasis Reviews, 2, 129–152.

    Google Scholar 

  31. Pavelic, K., Bulbul, M. A., Slocum, H. K., Pavelic, Z. P., Rustum, Y. M., Niedbala, M. J., and Bernacki, R. J., 1986, Growth of urological tumors on extracellular matrix as a model for in vitro cultivation of primary human tumor explants. Cancer Research, 46, 3653–3662.

    Google Scholar 

  32. Sacks, P. G., Wansor, K. J., and Parsons, D. F., 1984, Organ-cultured epithelial tissue as an in vitro model for invasion: quantitation and high voltage electron microscopy of tumor cell attachment. Cancer Research, 44, 3063–3074.

    Google Scholar 

  33. Sheela, S., and Barrett, J. C., 1982, In vitro degradation of radiolabelled, intact basement membrane mediated by cellular plasminogen activator. Carcinogenesis, 3, 363–369.

    Google Scholar 

  34. Siegal, G.P., Barsky, S. H., Terranova, V. P., and Liotta, L. A., 1981, Stages of neoplastic transformation of human breast tissue as monitored by dissolution of basement membrane components. Invasion and Metastasis, 1, 54–65.

    Google Scholar 

  35. Sloane, B. F., and Honk, K. V., 1984, Cysteine proteinases and metastasis. Cancer Metastasis Reviews, 3, 249–263.

    Google Scholar 

  36. Strauli, R., In-Albon, A., and Haemmerli, G., 1983, Morphological studies on V2 carcinoma invasion and tumor-associated connective tissue changes in the rabbit mesentery. Cancer Research, 43, 5403–5410.

    Google Scholar 

  37. Taylor, I. W., 1980, A rapid single-step staining technique for DNA analysis by microfluorometry. Journal of Histochemistry and Cytochemistry, 28, 1021–1024.

    Google Scholar 

  38. Tseng, S. C. G., Savion, N., Gospodarowicz, D., and Stern, R., 1981, Characterization of collagens synthesized by cultured bovine corneal endothelial cells. Journal of Biological Chemistry, 256, 3361–3365.

    Google Scholar 

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Authors and Affiliations

  1. Department of Experimental Therapeutics, Roswell Park Memorial Institute, 14263, Buffalo, New York, U.S.A.

    Michael J. Niedbala & Ralph J. Bernacki

  2. Department of Gynecology and Obstetrics, Buffalo General Hospital, 14263, Buffalo, New York, U.S.A.

    Kent Crickard

Authors
  1. Michael J. Niedbala
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  2. Kent Crickard
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  3. Ralph J. Bernacki
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Niedbala, M.J., Crickard, K. & Bernacki, R.J. In vitro degradation of extracellular matrix by human ovarian carcinoma cells. Clin Exp Metast 5, 181–197 (1987). https://doi.org/10.1007/BF00058063

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  • DOI: https://doi.org/10.1007/BF00058063

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