Skip to main content
Log in

C-met activation is necessary but not sufficient for liver colonization by B16 murine melanoma cells

  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

Metastasis to the liver is a frequent event in clinical oncology, the molecular mechanisms of which are not fully understood. We have recently reported a consistent overexpression of c-met in B16 melanoma cells selected in vivo for enhanced liver metastatic ability. In this study we address the question as to whether constitutive activation of c-met is a necessary and sufficient condition for enhanced liver colonization B16 melanoma cells. Different levels of c-met expression and/or activation in B16 cells were achieved subcloning, or by c-DNA transfection with either HGF/SF or the oncogenic form of c-met (tpr-met). Metastatic ability of the different populations was then evaluated in vivo by the lung colonization (experimental metastasis) assay. Results indicate that c-met (but not tpr-met) activation in B16 melanoma cells may increase their liver colonizing potential, probably by enhancing motility and invasion in response paracrine interactions with its ligand. C-met expres sion per se, however, is not able to change the organ specificity of the cells. C-met activation appears instead to be required at later stages of liver colonization by B16 melanoma cells, in order to enhance their site-specific metastatic ability. © Rapid Science 1998

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

Access this article

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. Kemeny NE, Kemeny M and Lawrence TS. 1995, Liver metastasis. In: Abeloff MD, Armitage JO, Lichter AS and Niederhuber JE, eds. Clinical Oncology. New York: Churchill Livingstone, pp. 679-707.

    Google Scholar 

  2. Fidler IJ and Hart IR. 1982, Biological diversity in metastatic neoplasms: origins and implications. Science, 217, 998-1003.

    PubMed  Google Scholar 

  3. Sargent NSE, Oestreicher M, Haidvogl H, Madnick HM and Burger MM. 1988, Growth regulation of cancer metastases by their host organ. Proc Natl Acad Sci USA, 85, 7251-55.

    PubMed  Google Scholar 

  4. Nicolson GL. 1991, Tumor and host molecules important in the organ preference of metastasis. Sem Cancer Biol, 2, 143-54.

    Google Scholar 

  5. Rusciano D and Burger MM. 1992, Why do cancer cells metastasize into particular organs? BioEssays, 14, 185-94.

    PubMed  Google Scholar 

  6. Nakamura T, Nishizawa T, Hagiya M et al.1989, Molecular cloning and expression of human hepatocyte growth factor. Nature, 342, 440-43.

    Article  PubMed  Google Scholar 

  7. Michalopoulos GK and Zarnegar R. 1992, Hepatocyte growth factor. Hepatol, 15, 150-55.

    Google Scholar 

  8. Zarnegar R and Michalopoulos GK. 1995, The many faces of Hepatocyte Growth Factor, from hepatopoiesis to hematopoiesis. J Cell Biol, 129, 1177-80.

    Article  PubMed  Google Scholar 

  9. Bottaro DP, Rubin JS, Faletto DL et al. 1991, Identification of the hepatocyte growth factor receptor as the c-metprotooncogene product. Science, 251, 802-4.

    PubMed  Google Scholar 

  10. Weidner KM, Sachs M and Birchmeier W. 1993, The met receptor tyrosine kinase transduces motility, proliferation and morphogenetic signals of scatter factor/hepatocyte growth factor in epithelial cells. J Cell Biol, 21, 145-54.

    Article  Google Scholar 

  11. Komada M and Kitamura N. 1993, The cell dissociation and motility triggered by scatter factor/hepatocyte growth factor are mediated through the cytoplasmic domain of the c-met receptor. Oncogene, 8, 2381-90.

    PubMed  Google Scholar 

  12. Rong S, Bodescot M, Blair D et al. 1992, Tumorigenicity of the met proto-oncogene and the gene for hepatocyte growth factor. Mol Cell Biol, 12, 5152-58.

    PubMed  Google Scholar 

  13. Rong S, Segal S, Anver M, Resau JH and Vande Woude GF. 1994, Invasiveness and metastasis of NIH 3T3 cells induced by met-hepatocyte growth factor/scatter factor autocrine stimulation. Proc Natl Acad Sci USA, 91, 4731-35.

    PubMed  Google Scholar 

  14. Giordano S, Zhen Z, Medico E, Gaudino G and Comoglio PM. 1993, Transfer of motogenic and invasive response to scatter factor/hepatocyte growth factor by transfection of human met proto-oncogene. Proc Natl Acad Sci USA, 90, 649-53.

    PubMed  Google Scholar 

  15. Rusciano D, Lorenzoni P and Burger MM. 1993, Paracrine growth response as a major determinant in liver-specific colonization by in vivoselected B16 murine melanoma cells. Invasion Metastasis, 13, 212-24.

    PubMed  Google Scholar 

  16. Rusciano D, Lorenzoni P and Burger MM. 1995, Expression of constitutively activated hepatocyte growth factor/scatter factor receptor (c-met) in B16 melanoma cells selected for enhanced liver colonization. Oncogene, 11, 1979-87.

    PubMed  Google Scholar 

  17. Rusciano D, Lorenzoni P and Burger MM. 1996, Constitutive activation of c-metin liver metastatic B16 melanoma cells depends on both substrate adhesion and cell density and is regulated by a cytosolic tyrosine phosphatase activity. J Biol Chem, 271, 20763-69.

    Article  PubMed  Google Scholar 

  18. Dean M, Park and Wande Woude GF. 1987, Characterization of the rearranged tpr-metoncogene breakpoint. Mol Cell Biol, 7, 921-24.

    PubMed  Google Scholar 

  19. Hartmann G, Naldini L, Weidner KM et al. 1992, A functional domain in the heavy chain of scatter factor/hepatocyte growth factor binds the c-met receptor and induces cell dissociation but not mitogenesis. Proc Natl Acad Sci USA, 89, 11574-78.

    PubMed  Google Scholar 

  20. Prat M, Narsimhan RP, Crepaldi T et al. 1991, The receptor encoded by the human c-met oncogene is expressed in hepatocytes, epithelial cells and solid tumors. Int J Cancer, 49, 323-28.

    PubMed  Google Scholar 

  21. Leoncini L, Pacenti L, Rusciano D et al. 1988, Correlation between differentiation and lung colonization by retinoic acid-treated F9 cells as revealed by the expression pattern of extracellular matrix and cell surface antigens. Am J Pathol, 130, 505-14.

    PubMed  Google Scholar 

  22. Wolf HK, Zarnegar R and Michalopoulos GK. 1991, Localization of hepatocyte growth factor in human and rat tissue. Hepatol, 14, 488-94.

    Article  Google Scholar 

  23. Tashiro K, Hagiya M, Nishizawa T et al. 1990, Deduced primary structure of rat hepatocyte growth factor and expression of the mRNA in rat tissue. Proc Natl Acad Sci USA, 87,3200-4.

    PubMed  Google Scholar 

  24. Kagoshima M, Kinoshita T, Matsumoto K and Nakamura T. 1992, Developmental changes in hepatocyte growth factor mRNA and its receptor in rat liver, kidney and lung. Eur J Biochem, 210, 375-380.

    PubMed  Google Scholar 

  25. Zarnegar R, DeFrances MC, Kost DP, Lindroos P and Michalopoulos GK. 1991, Expression of hepatocyte growth factor mRNA in regenerating rat liver after partial hepatectomy. Biochem Biophys Res Commum, 177, 559-65.

    Google Scholar 

  26. Yanagita K, Matsumoto K, Sekiguchi K et al. 1993, Hepatocyte growth factor may act as a pulmotrophic factor on lung regeneration after acute lung injury. J Biol Chem, 268, 21212-17.

    PubMed  Google Scholar 

  27. Kawaida K, Matsumoto K, Shimazu H and Nakamura T. 1994, Hepatocyte growth factor prevents renal failure and accelerates renal regeneration in mice. Proc Natl Acad Sci USA, 91, 4357-61.

    PubMed  Google Scholar 

  28. Tomiya T, Nagoshi S and Fujiwara K. 1992, Significance of serum hepatocyte growth factor levels in patients with hepatic failure. Hepatol, 15, 1-4.

    Article  Google Scholar 

  29. Yoshinaga Y, Matsuno Y, et al.1993, Immuno-histochemical detection of hepatocyte growth factor/scatter factor in human cancerous and inflammatory lesions of various organs. Jpn J Cancer Res, 84, 1150-58.

    Google Scholar 

  30. Eagles G, Warn A, Ball RY et al. 1996, Hepatocyte growth factor/scatter factor is present in most pleural effusion fluids from cancer patients. Br J Cancer, 73, 277-381.

    Google Scholar 

  31. Taniguchi T, Toi M, Inada K et al. 1995, Serum concentrations of hepatocyte growth factor in breast cancer patients. Clin Cancer Res, 1, 1031-34.

    PubMed  Google Scholar 

  32. Di Renzo MF, Narshiman RP, Olivero M et al. 1991, Expression of the Met/HGF receptor in normal and neoplastic human tissues. Oncogene, 6, 1997-2003.

    PubMed  Google Scholar 

  33. Radinsky R, Risin S, Fan D et al. 1995, Level and function of epidermal growth factor receptor predict the metastatic potential of human colon carcinoma cells. Clin Cancer Res, 1, 19-31.

    PubMed  Google Scholar 

  34. Grigioni WF, Fiorentino M, D'Errico A et al. 1995, Overexpression of c-metprotooncogene product and raised Ki67 index in hepatocellular carcinomas with respect to benign liver conditions. Hepatol, 21, 1543-46.

    Article  Google Scholar 

  35. Natali PG, Nicotra MR, Di Renzo MF et al. 1993, Expression of the C-Met/HGF receptor in human melanocytic neoplasms, demonstration of the relationship to malignant melanoma tumor progression. Br J Cancer, 68,746-50.

    PubMed  Google Scholar 

  36. Tuck AB, Park M, Sterns EE, Boag A and Elliott BE. 1996, Coexpression of Hepatocyte Growth Factor and receptor (met) in human breast carcinoma. Am J Pathol, 148, 225-32.

    PubMed  Google Scholar 

  37. Di Renzo MF, Olivero M, Katsaros D et al. 1994, Overexpression of the Met/HGF receptor in ovarian cancer. Int J Cancer, 58, 658-62.

    PubMed  Google Scholar 

  38. Hasegawa Y, Yamamoto M, Maeda S and Saitoh Y. 1995, Hepatocyte Growth Factor and its receptor cmetregulate both cell growth and invasion of human pancreatic cancer. Int J Oncol, 7, 877-81.

    Google Scholar 

  39. Humphrey PA, Zhu X, Zarnegar R et al. 1995, Hepatocyte Growth Factor and its receptor (c-met) in prostatic carcinoma. Am J Pathol, 147, 386-96.

    PubMed  Google Scholar 

  40. Ferracini R, Di Renzo MF, Scotlandi K et al. 1995, The MET/HGF receptor is overexpressed in human osteosarcomas and is activated by either a paracrine or an autocrine circuit. Oncogene, 10, 739-49.

    PubMed  Google Scholar 

  41. Di Renzo MF, Olivero M, Giacomini A et al. 1995, Overexpression and amplification of the Met/HGF receptor gene during the progression of colorectal cancer. Clin Cancer Res, 1, 147-54.

    PubMed  Google Scholar 

  42. Cooper CS, Park M, Blair DG et al. 1984, Molecular cloning of a new transforming gene from a chemically transformed human cell line. Nature, 311, 29-33.

    PubMed  Google Scholar 

  43. Soman NR, Correa P, Ruiz BA and Wogan GN. 1991, The tpr-met oncogenic rearrangement is present and expressed in human gastric carcinoma and precursor lesions. Proc Natl Acad Sci USA, 88, 4892-96.

    PubMed  Google Scholar 

  44. Soman NR, Wogan GN and Rhim JS. 1990, Tpr-metoncogenic rearrangement, detection by pcr amplification of the transcript and expression in human tumor cell lines. Proc Natl Acad Sci USA, 87, 738-42.

    PubMed  Google Scholar 

  45. Gonzatti-Haces M, Seth A, Park M et al. 1988, Characterization of the TPR-MET oncogene p65 and the MET protooncogene p140 protein-tyrosine kinases. Proc Natl Acad Sci USA, 85, 21-25.

    PubMed  Google Scholar 

  46. Jeffers M, Rong S and Vande Woude GF. 1996, Enhanced tumorigenicity and invasion-metastasis by HGF/SF-met signalling in human cells concomitant with induction of the urokinase proteolysis network. Mol Cell Biol, 16, 1115-25.

    PubMed  Google Scholar 

  47. Yayon A and Klagsbrun M. 1990, Autocrine regulation of cell growth and transformation by basic fibroblast growth factor. Cancer Metastasis Rev, 9, 191-202.

    PubMed  Google Scholar 

  48. Damen JE, Greenberg AH and Wright JA. 1991, Transformation and amplification of the K-fgf protooncogene in NIH3T3 cells, and induction of metastatic potential. Biochim Biophys Acta, 1097, 103-10.

    PubMed  Google Scholar 

  49. Yu D, Hamada J, Zhang H, Nicolson GL and Hung MC. 1992, Mechanisms of c-erbB2/neuoncogene-induced metastasis and repression of metastatic properties by adenovirus 5 E1A gene products. Oncogene, 7, 2263-70.

    Google Scholar 

  50. Yu D, Wang SS, Dulski KM et al. 1994, C-erbB2/neuoverexpression enhances metastatic potential of human lung cancer cells by induction of metastasis-associated properties. Cancer Res, 54, 3260-66.

    PubMed  Google Scholar 

  51. Guy CT, Webster MA, Schaller M et al.1992, Expression of the neuprotooncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc Natl Acad Sci USA, 89, 10578-82.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lin, S., Rusciano, D., Lorenzoni, P. et al. C-met activation is necessary but not sufficient for liver colonization by B16 murine melanoma cells. Clin Exp Metastasis 16, 253–265 (1998). https://doi.org/10.1023/A:1006596909948

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006596909948

Navigation