Biological role of the HGF/MET ligand/receptor couple in bovine mammary epithelial cells

The mammary gland is an organ in which numerous remodelling events follow each other during the development and the reproductive cycle of the animal. After puberty and during pregnancy morphogenesis and proliferation transform the primordial epithelium to an extended network composed of hollow tubules and secreting acini. The development of the mammary gland requires several locally-derived growth factors such Hepatocyte Growth Factor (HGF). Hepatocyte Growth Factor (HGF) is a cytokine originally described as a mitogenic factor for hepatocytes during liver regeneration. HGF is secreted by mesenchymal/stromal cells and acts as a paracrine factor on adjacent epithelial cells that express the c-met tyrosine kinase receptor (Sonnenberg et al., 1993). Binding of HGF to its receptor induces multiple biological responses including proliferation, motility, invasion of the extracellular matrix, resistance to apoptosis and activation of angiogenesis (Bussolino et al., 1992; Brinkmann et al., 1995; Bardelli et al., 1996; Medico et al., 1996). HGF and c-met are expressed and temporally regulated during mammary development and differentiation; some mammary epithelial cell lines grown in a three dimensional collagen matrix with HGF generate tubules (Soriano et al., 1995) with a morphology resembling mammary ducts. Recently, bovine HGF and c-met have been analyzed for their expression in the mammary gland, but no data regarding their biological roles are yet available. We have therefore investigated whether the bovine mammary epithelial cell line BME-UV1 was responsive to HGF and what the biological effects induced by this cytokine were