The role of hepatocyte growth factor and its receptor c-Met in multiple myeloma and other blood malignancies

The cytokine hepatocyte growth factor (HGF) and its receptor c-Met are a li gand-receptor pair with important functions in a communicative interplay be tween HGF-producing, mesenchymal cells and c-Met-expressing, target cells. HGF is cytoprotective and causes regeneration of parenchyma after tissue da mage in several organs. The receptor c-Met was first characterized as an on cogene product being responsible for the transformation of an osteosarcoma cell line. KGF or c-Met is overexpressed in several human cancers, includin g various carcinomas. Some cells of hematopoietic origin also seem to be ca pable of c-Met expression, but the precise role of HGF in normal hematopoie sis is yet to be determined. In blood malignancies like acute myelogenous l eukemia and, notably, multiple myeloma, HGF is overproduced and has implica tions for the prognosis of the patients. Biological significance of HGF ove rexpression in multiple myeloma is discussed and is likely to include effec ts on bone turnover and angiogenesis.