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Identification of HGF/Met regulated genes: Implications for HGF/Met-mediated cell invasion and metastasis

  1. Author:
    Taylor, G. A.
    Jeffers, M.
    Webb, C. P.
    Vande Woude, G. F.
    1. Year of Conference: 1997
  2. Conference Name: Annual Meeting of the American Association for Cancer Research
    1. 38
    2. Pages: A1936
  4. Type of Work: Meeting Abstract
  1. Abstract:

    Hepatocyte growth factor (HGF) is a pleiotropic effector of cells expressing its receptor, the Met tyrosine kinase. While HGF expression is normally restricted to mesenchymal cells and Met expression to epithelial cells, coexpression of HGF and Met in mesenchymal cells can lead to changes in cellular morphology in vitro, formation of branching structures in matrigel cultures, and increased tumorigenic, invasive, and metastatic capabilities in nude mice. We have begun to address the molecular basis for these phenomena, by using differential display screening to identify changes in gene expression in SK-LMS-1 human leiomyosarcoma cells that were engineered to coexpress HGF and Met. We noted decreases in fibronectin and transforming growth factor b expression and increases in integrin a6 expression. Similar changes were noted in other human tumors and transformed mouse fibroblasts that also contained an HGF/Met autocrine loop. Our results define changes in cell-extracellular matrix interactions that underlie HGF/Met-mediated cell motility and migration.

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