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Hepatocyte growth factor and the Met system as a mediator of tumor–stromal interactions
Author(s) -
Matsumoto Kunio,
Nakamura Toshikazu
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21808
Subject(s) - hepatocyte growth factor , stromal cell , paracrine signalling , cancer research , receptor tyrosine kinase , biology , cancer associated fibroblasts , tyrosine kinase , stroma , mediator , cancer cell , cancer , tumor microenvironment , pathology , microbiology and biotechnology , immunology , medicine , receptor , signal transduction , immunohistochemistry , genetics , tumor cells
Crosstalk between carcinoma cells and host stromal cells such as fibroblasts has a great deal of influence on the invasive and metastatic behavior of cancer cells. The oncogenic action of fibroblasts has been demonstrated through genetic alterations that occur specifically in fibroblasts. Hepatocyte growth factor (HGF), a ligand for the Met receptor tyrosine kinase, plays a definitive role, particularly in the progression to invasive and metastatic cancers, predominantly as a stroma‐derived paracrine mediator. Many types of cancer cells secrete molecules that enhance HGF production in fibroblasts, while fibroblast‐derived HGF, in turn, is a potent stimulator of the invasion of cancer cells. Fibroblast‐specific genetic alterations leading to an overexpression of HGF are associated with the development of epithelial neoplasia and invasive carcinoma. Strategies for targeting the HGF–Met axis are being pursued, in attempts to block the malignant behavior of cancers. In normal tissues, the HGF–Met axis plays diverse roles in organogenesis and in wound healing. The simile that “cancer is a never‐healing wound” appears to be pertinent here. © 2006 Wiley‐Liss, Inc.