Abstract
Hepatocyte growth factor (HGF)/scatter factor (SF) is a cytokine which is produced by mesenchymal cells and stimulates the motility of some epithelial cells, including cancer cells and vascular endothelial cells. Two human lung cancer cell lines, PC‐1 and PC‐13, were found to produce a protein which was indistinguishable from HGF/SF with regard to biological activities and immunological characteristics, although they were derived from epithelial cells. In general, highly aggressive cancer cells often show some mesenchymal characteristics, and production of HGF/SF by cancer cells is also considered as a phenomenon of acquisition of mesenchymal phenotype, which may be involved in cancer invasion and progression. These cell lines showed no apparent response to exogenous HGF/SF. In addition, no c‐met proto‐oncogene product was detectable in these cells by Western blot analysis. Although the function of HGF/SF produced by cancer cells, either autocrine or paracrine stimulation, remains to be studied, this is the first report to describe cancer cells producing HGF/SF.
Keywords: Hepatocyte growth factor, Scatter factor, Tumor invasion, Angiogenesis
Full Text
The Full Text of this article is available as a PDF (573.5 KB).
REFERENCES
- 1. ) Lam , W. C. , Delikatny , E. J. , Orr , F. W. , Wass , J , Vaani , J. and Ward , P. A.The chemotactic response of tumor cells: a model for cancer metastasis . Am. J. Pathol , 104 , 69 – 76 ( 1981. ). [PMC free article] [PubMed] [Google Scholar]
- 2. ) Liotta , L. A.Tumor invasion and metastasis ‐ role of the extracellular matrix: Rhoads Memorial Award Lecture . Cancer Res. , 46 , 1 – 7 ( 1986. ). [PubMed] [Google Scholar]
- 3. ) Yoshida , K. , Ozaki , T. , Ushijima , K. and Hayashi , H.Studies on the mechanisms of invasion in cancer: isolation and purification of a factor chemotactic for cancer cells . Int. J. Cancer , 6 , 123 – 132 ( 1970. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Liotta , L. A. , Mandler , R. , Murano , G. , Katz , D. A. , Gordon , R. K. , Chiang , P. K. and Schiffmann , E.Tumor cell autocrine motility factor . Proc. Natl. Acad. Sci. USA , 83 , 3302 – 3306 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. ) Guirguis , R. , Schiffmann , E. , Liu , B. , Birkbeck , D. , Engel , J. and Liotta , L. A.Detection of autocrine motility factor in urine as a marker of bladder cancer . J. Natl. Cancer Inst , 80 , 1203 – 1211 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 6. ) Grey , A. M. , Schor , A. M. , Rushton , G. , Ellis , I. and Schor , S. L.Purification of the migration stimulating factor produced by fetal and breast cancer patient fibro‐blasts . Proc. Natl. Acad. Sci. USA , 86 , 2438 – 2442 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. ) Stoker , M. , Gherardi , E. , Perryman , M. and Gray , J.Scatter factor is a fibroblast‐derived modulator of epithelial cell mobility . Nature , 327 , 239 – 242 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 8. ) Weidner , K. M. , Behrens , J. , Vandekerckhove , J. and Birchmeier , W.Scatter factor: molecular characteristics and effect on the invasiveness of epithelial cells . J. Celt Biol , 111 , 2097 – 2108 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. ) Rosen , E. M. , Meromsky , L. , Setter , E. , Vinter , D. W. and Goldberg , I. D.Purified scatter factor stimulates epithelial and vascular endothelial cell migration . Proc. Soc. Exp. Biol. Med , 195 , 34 – 43 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 10. ) Nakamura , T. , Nawa , K. and Ichihara , A.Partial purification and characterization of hepatocyte growth factor from serum of hepatectomized rats . Biochem. Biophys. Res. Commun. , 122 , 1450 – 1459 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 11. ) Nakamura , T. , Nishizawa , T. , Hagiya , M. , Seki , T. , Shimonishi , M. , Sugimura , A. , Tashiro , K. and Shimizu , S.Molecular cloning and expression of human hepatocyte growth factor . Nature , 342 , 440 – 443 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 12. ) Igawa , T. , Kanda , S. , Kanetake , H. , Saitoh , Y. , Ichihara , A. , Tomita , Y. and Nakamura , T.Hepatocyte growth factor is a potent mitogen for cultured rabbit renal tubular epithelial cells . Biochem. Biophys. Res. Commun , 174 , 831 – 838 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 13. ) Kan , M. , Zhang , G. , Zarnegar , R. , Michalopoulos , G. , Myoken , Y. , Mekeehan , W. L. and Stevens , J. I.Hepatocyte growth factor/hepatopoietin A stimulates the growth of rat kidney proximal tubule epithelial cells (RPTE), rat nonparenchymal liver cells, human melanoma cells, mouse keratinocytes and stimulates anchorage‐independent growth of SV‐40 transformed RPTE . Biochem. Biophys. Res. Commun. , 174 , 331 – 337 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 14. ) Nakamura , T.Structure and function of hepatocyte growth factor . Prog. Growth Factor Res. , 3 , 67 – 85 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 15. ) Matsumoto , K. and Nakamura , T.Hepatocyte growth factor: molecular structure, roles in liver regeneration, and other biological functions . Crit. Rev. Oncogenesis , 3 , 27 – 54 ( 1992. ). [PubMed] [Google Scholar]
- 16. ) Gherardi , E. and Stoker , M.Hepatocyte growth factor‐scatter factor: mitogen, motogen, and met . Cancer Cells , 3 , 227 – 232 ( 1991. ). [PubMed] [Google Scholar]
- 17. ) Noji , S. , Tashiro , K. , Koyama , E. , Nohno , T. , Ohyama , K. , Taniguchi , S. and Nakamura , T.Expression of hepatocyte growth factor gene in endothelial and Kupffer cells of damaged rat livers, as revealed by in situ hybridization . Biochem. Biophys. Res. Commun. , 173 , 42 – 47 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 18. ) Adams , J. C. , Furlong , R. A. and Watt , F. M.Production of scatter factor by ndk, a strain of epithelial cells, and inhibition of scatter factor activity by suramin . J. Cell Sci , 98 , 385 – 394 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 19. ) Nakamura , H. , Odaka , T. , Takahashi , E. , Kobayashi , T. , Saito , M. , Takahashi , H. , Matsushima , Y. , Konaka , C. and Kato , H.Effects of long‐term culture in vitro on human lung cancer cell line . Lung Cancer , 31 , 503 – 510 ( 1991. ) ( in Japanese ). [Google Scholar]
- 20. ) Konishi , T. , Takehara , T. , Tsuji , T. , Ohsato , K. , Matsumoto , K. and Nakamura , T.Scatter factor from human embryonic lung fibroblasts is probably identical to hepatocyte growth factor . Biochem. Biophys. Res. Commun. , 180 , 765 – 773 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 21. ) Bottaro , D. P. , Rubin , J. S. , Faletto , D. L. , Chan , A. M. L. , Kmiecik , T. E. , Vande Woude , G. F. and Aaronson , S. A.Identification of the hepatocyte growth factor receptor as the c‐met proto‐oncogene product . Science , 251 , 802 – 804 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 22. ) Stoker , M. and Perryman , M.An epithelial scatter factor released by embryo ftbroblasts . J. Cell Sci. , 77 , 209 – 223 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 23. ) Seki , T. , Ihara , I. , Sugimura , A. , Shimonishi , M. , Nishizawa , T. , Asami , O. , Hagiya , MN. , Nakamura , T. and Shimizu , S.Isolation and expression of cDNA for different forms of hepatocyte growth factor from human leukocyte . Biochem. Biophys. Res. Commun. , 172 , 321 – 327 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 24. ) Laemmli , U. K.Cleavage of structural proteins during the assembly of the head of bacteriophage T4 . Nature , 227 , 680 – 685 ( 1970. ). [DOI] [PubMed] [Google Scholar]
- 25. ) Upton , M. P. , Hirohashi , S. , Tome , Y. , Miyazawa , N. , Suemasu , K. and Shimosato , Y.Expression of vimentin in surgically resected adenocarcinomas and large cell carcinomas of lung . Am. J. Surg. Pathol , 10 , 560 – 567 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 26. ) Naldini , L. , Weidner , K. M. , Vigna , E. , Gaudino , G. , Bardelli , A. , Panzetto , C. , Narsimhan , R. P. , Hartmann , G. , Zarnegar , R. , Michalopoulos , G. K. , Birchmeier , W. and Comoglio , P. M.Scatter factor and hepatocyte growth factor are indistinguishable ligands for the met receptor . EMBO J. , 10 , 2867 – 2878 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. ) Browder , T. M. , Dunbar , C. E. and Nienhuis , A. W.Private and public autocrine loops in neoplastic cells . Cancer Cells , 1 , 9 – 17 ( 1989. ). [PubMed] [Google Scholar]