Autocrine hepatocyte growth factor/scatter factor signaling induces transformation and the invasive/metastatic phenotype in C127 cells

Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic effector for cells expressing the Met tyrosine kinase receptor. In this investigation, we show that pancreatic oval cells express Met and exhibit a proliferative response to HGF/SF. Additionally, we found that oval cells treated transiently with this factor become “scattered, ” whereas those exposed to HGF/ SF for extended periods of time form branching tubular structures. These structures possess true lumens, which are lined by cells with ductal features, including apical microvilli, well-developed intercellular junctions, interdigitation of plasma membranes, and abundant cytoplasmic organelles. Interestingly, these ductal structures are formed by HGF/SF-treated cells cultured on plastic dishes in the absence of exogenous extracellular matrix components. Consistent with their ability to form ductal structures in vitro, we found that pancreatic oval cells form ductal adenocarcinomas in nude mice. This study supports the involvement of HGF/SF-Met signaling in the growth, migration, and morphogenesis of pancreatic oval cells and may have important implications for the expansion and morphogenic differentiation of these cells during developmental, regenerative, and neoplastic growth