Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1994 Dec 2;127(6):1783–1787. doi: 10.1083/jcb.127.6.1783

Scatter factor and the c-met receptor: a paradigm for mesenchymal/epithelial interaction

PMCID: PMC2120304  PMID: 7806559

Abstract

Epithelia and mesenchyme interact during various physiologic and pathologic processes. Scatter factor is a mesenchyme-derived cytokine that stimulates motility, proliferation, and morphogenesis of epithelia. Recent studies suggest that scatter factor and its receptor (c-met) mediate mesenchyme/epithelia signalling and even interconversion. In this mini-review, we will discuss how scatter factor and c-met may mediate interactions between mesenchyme and epithelia during embryogenesis, organ repair, and neoplasia.

Full Text

The Full Text of this article is available as a PDF (607.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bhargava M., Joseph A., Knesel J., Halaban R., Li Y., Pang S., Goldberg I., Setter E., Donovan M. A., Zarnegar R. Scatter factor and hepatocyte growth factor: activities, properties, and mechanism. Cell Growth Differ. 1992 Jan;3(1):11–20. [PubMed] [Google Scholar]
  2. Birchmeier W., Weidner K. M., Hülsken J., Behrens J. Molecular mechanisms leading to cell junction (cadherin) deficiency in invasive carcinomas. Semin Cancer Biol. 1993 Aug;4(4):231–239. [PubMed] [Google Scholar]
  3. Bottaro D. P., Rubin J. S., Faletto D. L., Chan A. M., Kmiecik T. E., Vande Woude G. F., Aaronson S. A. Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science. 1991 Feb 15;251(4995):802–804. doi: 10.1126/science.1846706. [DOI] [PubMed] [Google Scholar]
  4. Chan A. M., Rubin J. S., Bottaro D. P., Hirschfield D. W., Chedid M., Aaronson S. A. Identification of a competitive HGF antagonist encoded by an alternative transcript. Science. 1991 Nov 29;254(5036):1382–1385. doi: 10.1126/science.1720571. [DOI] [PubMed] [Google Scholar]
  5. Gandino L., Di Renzo M. F., Giordano S., Bussolino F., Comoglio P. M. Protein kinase-c activation inhibits tyrosine phosphorylation of the c-met protein. Oncogene. 1990 May;5(5):721–725. [PubMed] [Google Scholar]
  6. Gherardi E., Gray J., Stoker M., Perryman M., Furlong R. Purification of scatter factor, a fibroblast-derived basic protein that modulates epithelial interactions and movement. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5844–5848. doi: 10.1073/pnas.86.15.5844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gohda E., Matsunaga T., Kataoka H., Yamamoto I. TGF-beta is a potent inhibitor of hepatocyte growth factor secretion by human fibroblasts. Cell Biol Int Rep. 1992 Sep;16(9):917–926. doi: 10.1016/s0309-1651(06)80171-2. [DOI] [PubMed] [Google Scholar]
  8. Gonzatti-Haces M., Seth A., Park M., Copeland T., Oroszlan S., Vande Woude G. F. Characterization of the TPR-MET oncogene p65 and the MET protooncogene p140 protein-tyrosine kinases. Proc Natl Acad Sci U S A. 1988 Jan;85(1):21–25. doi: 10.1073/pnas.85.1.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Grant D. S., Kleinman H. K., Goldberg I. D., Bhargava M. M., Nickoloff B. J., Kinsella J. L., Polverini P., Rosen E. M. Scatter factor induces blood vessel formation in vivo. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1937–1941. doi: 10.1073/pnas.90.5.1937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Huff J. L., Jelinek M. A., Borgman C. A., Lansing T. J., Parsons J. T. The protooncogene c-sea encodes a transmembrane protein-tyrosine kinase related to the Met/hepatocyte growth factor/scatter factor receptor. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6140–6144. doi: 10.1073/pnas.90.13.6140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kamalati T., Thirunavukarasu B., Wallace A., Holder N., Brooks R., Nakamura T., Stoker M., Gherardi E., Buluwela L. Down-regulation of scatter factor in MRC 5 fibroblasts by epithelial-derived cells. A model for scatter factor modulation. J Cell Sci. 1992 Feb;101(Pt 2):323–332. doi: 10.1242/jcs.101.2.323. [DOI] [PubMed] [Google Scholar]
  12. Kawaida K., Matsumoto K., Shimazu H., Nakamura T. Hepatocyte growth factor prevents acute renal failure and accelerates renal regeneration in mice. Proc Natl Acad Sci U S A. 1994 May 10;91(10):4357–4361. doi: 10.1073/pnas.91.10.4357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Koch C. A., Anderson D., Moran M. F., Ellis C., Pawson T. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science. 1991 May 3;252(5006):668–674. doi: 10.1126/science.1708916. [DOI] [PubMed] [Google Scholar]
  14. Liu Y., Michalopoulos G. K., Zarnegar R. Structural and functional characterization of the mouse hepatocyte growth factor gene promoter. J Biol Chem. 1994 Feb 11;269(6):4152–4160. [PubMed] [Google Scholar]
  15. Miyazawa K., Shimomura T., Kitamura A., Kondo J., Morimoto Y., Kitamura N. Molecular cloning and sequence analysis of the cDNA for a human serine protease reponsible for activation of hepatocyte growth factor. Structural similarity of the protease precursor to blood coagulation factor XII. J Biol Chem. 1993 May 15;268(14):10024–10028. [PubMed] [Google Scholar]
  16. Miyazawa K., Shimomura T., Naka D., Kitamura N. Proteolytic activation of hepatocyte growth factor in response to tissue injury. J Biol Chem. 1994 Mar 25;269(12):8966–8970. [PubMed] [Google Scholar]
  17. Miyazawa K., Tsubouchi H., Naka D., Takahashi K., Okigaki M., Arakaki N., Nakayama H., Hirono S., Sakiyama O., Takahashi K. Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor. Biochem Biophys Res Commun. 1989 Sep 15;163(2):967–973. doi: 10.1016/0006-291x(89)92316-4. [DOI] [PubMed] [Google Scholar]
  18. Montesano R., Matsumoto K., Nakamura T., Orci L. Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor. Cell. 1991 Nov 29;67(5):901–908. doi: 10.1016/0092-8674(91)90363-4. [DOI] [PubMed] [Google Scholar]
  19. Naidu Y. M., Rosen E. M., Zitnick R., Goldberg I., Park M., Naujokas M., Polverini P. J., Nickoloff B. J. Role of scatter factor in the pathogenesis of AIDS-related Kaposi sarcoma. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5281–5285. doi: 10.1073/pnas.91.12.5281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nakamura T., Nishizawa T., Hagiya M., Seki T., Shimonishi M., Sugimura A., Tashiro K., Shimizu S. Molecular cloning and expression of human hepatocyte growth factor. Nature. 1989 Nov 23;342(6248):440–443. doi: 10.1038/342440a0. [DOI] [PubMed] [Google Scholar]
  21. Noji S., Tashiro K., Koyama E., Nohno T., Ohyama K., Taniguchi S., 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. 1990 Nov 30;173(1):42–47. doi: 10.1016/s0006-291x(05)81018-6. [DOI] [PubMed] [Google Scholar]
  22. Pavalko F. M., Otey C. A. Role of adhesion molecule cytoplasmic domains in mediating interactions with the cytoskeleton. Proc Soc Exp Biol Med. 1994 Apr;205(4):282–293. doi: 10.3181/00379727-205-43709. [DOI] [PubMed] [Google Scholar]
  23. Pepper M. S., Matsumoto K., Nakamura T., Orci L., Montesano R. Hepatocyte growth factor increases urokinase-type plasminogen activator (u-PA) and u-PA receptor expression in Madin-Darby canine kidney epithelial cells. J Biol Chem. 1992 Oct 5;267(28):20493–20496. [PubMed] [Google Scholar]
  24. Ponzetto C., Bardelli A., Zhen Z., Maina F., dalla Zonca P., Giordano S., Graziani A., Panayotou G., Comoglio P. M. A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. Cell. 1994 Apr 22;77(2):261–271. doi: 10.1016/0092-8674(94)90318-2. [DOI] [PubMed] [Google Scholar]
  25. Rong S., Bodescot M., Blair D., Dunn J., Nakamura T., Mizuno K., Park M., Chan A., Aaronson S., Vande Woude G. F. Tumorigenicity of the met proto-oncogene and the gene for hepatocyte growth factor. Mol Cell Biol. 1992 Nov;12(11):5152–5158. doi: 10.1128/mcb.12.11.5152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ronsin C., Muscatelli F., Mattei M. G., Breathnach R. A novel putative receptor protein tyrosine kinase of the met family. Oncogene. 1993 May;8(5):1195–1202. [PubMed] [Google Scholar]
  27. Rosen E. M., Goldberg I. D., Liu D., Setter E., Donovan M. A., Bhargava M., Reiss M., Kacinski B. M. Tumor necrosis factor stimulates epithelial tumor cell motility. Cancer Res. 1991 Oct 1;51(19):5315–5321. [PubMed] [Google Scholar]
  28. Rosen E. M., Joseph A., Jin L., Rockwell S., Elias J. A., Knesel J., Wines J., McClellan J., Kluger M. J., Goldberg I. D. Regulation of scatter factor production via a soluble inducing factor. J Cell Biol. 1994 Oct;127(1):225–234. doi: 10.1083/jcb.127.1.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rosen E. M., Knesel J., Goldberg I. D., Jin L., Bhargava M., Joseph A., Zitnik R., Wines J., Kelley M., Rockwell S. Scatter factor modulates the metastatic phenotype of the EMT6 mouse mammary tumor. Int J Cancer. 1994 Jun 1;57(5):706–714. doi: 10.1002/ijc.2910570517. [DOI] [PubMed] [Google Scholar]
  30. Rosen E. M., Meromsky L., Goldberg I., Bhargava M., Setter E. Studies on the mechanism of scatter factor. Effects of agents that modulate intracellular signal transduction, macromolecule synthesis and cytoskeleton assembly. J Cell Sci. 1990 Aug;96(Pt 4):639–649. doi: 10.1242/jcs.96.4.639. [DOI] [PubMed] [Google Scholar]
  31. Rosen E. M., Meromsky L., Setter E., Vinter D. W., Goldberg I. D. Purified scatter factor stimulates epithelial and vascular endothelial cell migration. Proc Soc Exp Biol Med. 1990 Oct;195(1):34–43. doi: 10.3181/00379727-195-43115. [DOI] [PubMed] [Google Scholar]
  32. Rubin J. S., Chan A. M., Bottaro D. P., Burgess W. H., Taylor W. G., Cech A. C., Hirschfield D. W., Wong J., Miki T., Finch P. W. A broad-spectrum human lung fibroblast-derived mitogen is a variant of hepatocyte growth factor. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):415–419. doi: 10.1073/pnas.88.2.415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Santos O. F., Barros E. J., Yang X. M., Matsumoto K., Nakamura T., Park M., Nigam S. K. Involvement of hepatocyte growth factor in kidney development. Dev Biol. 1994 Jun;163(2):525–529. doi: 10.1006/dbio.1994.1169. [DOI] [PubMed] [Google Scholar]
  34. Santos O. F., Nigam S. K. HGF-induced tubulogenesis and branching of epithelial cells is modulated by extracellular matrix and TGF-beta. Dev Biol. 1993 Dec;160(2):293–302. doi: 10.1006/dbio.1993.1308. [DOI] [PubMed] [Google Scholar]
  35. Schwartz M. A. Transmembrane signalling by integrins. Trends Cell Biol. 1992 Oct;2(10):304–308. doi: 10.1016/0962-8924(92)90120-c. [DOI] [PubMed] [Google Scholar]
  36. Seslar S. P., Nakamura T., Byers S. W. Regulation of fibroblast hepatocyte growth factor/scatter factor expression by human breast carcinoma cell lines and peptide growth factors. Cancer Res. 1993 Mar 15;53(6):1233–1238. [PubMed] [Google Scholar]
  37. Shibamoto S., Hayakawa M., Takeuchi K., Hori T., Oku N., Miyazawa K., Kitamura N., Takeichi M., Ito F. Tyrosine phosphorylation of beta-catenin and plakoglobin enhanced by hepatocyte growth factor and epidermal growth factor in human carcinoma cells. Cell Adhes Commun. 1994 Jan;1(4):295–305. doi: 10.3109/15419069409097261. [DOI] [PubMed] [Google Scholar]
  38. Sonnenberg E., Meyer D., Weidner K. M., Birchmeier C. Scatter factor/hepatocyte growth factor and its receptor, the c-met tyrosine kinase, can mediate a signal exchange between mesenchyme and epithelia during mouse development. J Cell Biol. 1993 Oct;123(1):223–235. doi: 10.1083/jcb.123.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Stoker M., Gherardi E., Perryman M., Gray J. Scatter factor is a fibroblast-derived modulator of epithelial cell mobility. Nature. 1987 May 21;327(6119):239–242. doi: 10.1038/327239a0. [DOI] [PubMed] [Google Scholar]
  40. Stoker M. Junctional competence in clones of mammary epithelial cells, and modulation by conditioned medium. J Cell Physiol. 1984 Oct;121(1):174–183. doi: 10.1002/jcp.1041210122. [DOI] [PubMed] [Google Scholar]
  41. Tamura M., Arakaki N., Tsubouchi H., Takada H., Daikuhara Y. Enhancement of human hepatocyte growth factor production by interleukin-1 alpha and -1 beta and tumor necrosis factor-alpha by fibroblasts in culture. J Biol Chem. 1993 Apr 15;268(11):8140–8145. [PubMed] [Google Scholar]
  42. Tsarfaty I., Resau J. H., Rulong S., Keydar I., Faletto D. L., Vande Woude G. F. The met proto-oncogene receptor and lumen formation. Science. 1992 Aug 28;257(5074):1258–1261. doi: 10.1126/science.1387731. [DOI] [PubMed] [Google Scholar]
  43. Tsarfaty I., Rong S., Resau J. H., Rulong S., da Silva P. P., Vande Woude G. F. The Met proto-oncogene mesenchymal to epithelial cell conversion. Science. 1994 Jan 7;263(5143):98–101. doi: 10.1126/science.7505952. [DOI] [PubMed] [Google Scholar]
  44. Tsukita S., Oishi K., Akiyama T., Yamanashi Y., Yamamoto T., Tsukita S. Specific proto-oncogenic tyrosine kinases of src family are enriched in cell-to-cell adherens junctions where the level of tyrosine phosphorylation is elevated. J Cell Biol. 1991 May;113(4):867–879. doi: 10.1083/jcb.113.4.867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Weidner K. M., Arakaki N., Hartmann G., Vandekerckhove J., Weingart S., Rieder H., Fonatsch C., Tsubouchi H., Hishida T., Daikuhara Y. Evidence for the identity of human scatter factor and human hepatocyte growth factor. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7001–7005. doi: 10.1073/pnas.88.16.7001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Weidner K. M., Sachs M., Birchmeier W. The Met receptor tyrosine kinase transduces motility, proliferation, and morphogenic signals of scatter factor/hepatocyte growth factor in epithelial cells. J Cell Biol. 1993 Apr;121(1):145–154. doi: 10.1083/jcb.121.1.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Yamashita J., Ogawa M., Yamashita S., Nomura K., Kuramoto M., Saishoji T., Shin S. Immunoreactive hepatocyte growth factor is a strong and independent predictor of recurrence and survival in human breast cancer. Cancer Res. 1994 Apr 1;54(7):1630–1633. [PubMed] [Google Scholar]
  48. Yanagita K., Nagaike M., Ishibashi H., Niho Y., Matsumoto K., Nakamura T. Lung may have an endocrine function producing hepatocyte growth factor in response to injury of distal organs. Biochem Biophys Res Commun. 1992 Jan 31;182(2):802–809. doi: 10.1016/0006-291x(92)91803-x. [DOI] [PubMed] [Google Scholar]
  49. Yoshimura T., Yuhki N., Wang M. H., Skeel A., Leonard E. J. Cloning, sequencing, and expression of human macrophage stimulating protein (MSP, MST1) confirms MSP as a member of the family of kringle proteins and locates the MSP gene on chromosome 3. J Biol Chem. 1993 Jul 25;268(21):15461–15468. [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES