Hepatocyte growth factor and Madin-Darby canine kidney cells: in vitro models of epithelial cell movement and morphogenesis.

It is becoming increasingly apparent that epithelial cell movement and changes in morphology are central to both development and regeneration of epithelial organs and are involved with pathological processes such as transformation of epithelia to carcinoma and metastasis. Hepatocyte growth factor (HGF) is a mesenchymally derived growth factor with pleiotrophic effects on epithelia depending on culture conditions. In vivo, HGF plays a role in mesenchymal-epithelial interactions. Madin-Darby canine kidney (MDCK) cells, which share many properties with polarized epithelia in vivo, are remarkably sensitive to HGF. In vitro models of HGF-treated MDCK cells have proven to be useful for the study of epithelial cell movement and changes in morphology. When cultured on plastic at low density, MDCK cells scatter in response to HGF. MDCK cells grown as cell suspensions in collagen gels form complex branching tubular structures in response to HGF. When cultivated as a monolayer on permeant supports, MDCK cells are well polarized with established E-cadherin mediated cell-cell junctions and dedifferentiate in response to HGF. Some of the mechanisms responsible for changes in cell movement and morphology that have been characterized using these models are summarized in this review. Models of MDCK cells exposed to HGF will continue to be useful in the study of epithelial cell movement and morphogenesis in vitro and will provide important clues into the cellular mechanisms important during in vivo epithelial processes such as organ development, regeneration, and transformation to carcinoma.