Cytokines facilitate chemotactic motility of breast carcinoma cells

Specific tissue interactions between epithelia and mesenchyme (or stroma), e.g., epithelial-mesenchymal (or -stromal) interactions mediate crucial aspects of normal development and tissue regeneration. These events affect tissue induction, organogenesis, cell movement, and morphogenesis of multicellular structures. Extensive and diverse studies have established that hepatocyte growth factor (HGF), a ligand for the c-met protooncogene product of receptor tyrosine kinase, is a mesenchymal- or stromal-derived multipotent polypeptide which mediates epithelial-mesenchymal interactions. During embryogenesis, HGF supports organogenesis and morphogenesis of various tissues and organs, including the liver, kidney, lung, gut, mammary gland, tooth, skeletal system, etc. In adult tissues, HGF elicits a potent organotrophic function which supports regeneration of organs including the liver, kidney, and lung. In the brain, HGF is a new member of the family of neurotrophic factors. In neoplastic tissue, HGF is involved in tumor invasion and metastasis, through tumor-stromal interactions. While HGF was originally identified as a potent mitogen for mature hepatocytes, the biological functions of this factor reach far beyond the original identifications. Such being the case, use of HGF for purposes of therapeutics is being given increasing attention.

Scatter factor (SF), a secretory protein of fibroblasts, dissociates and increases the motility of epithelial cells and may be involved in cell migration processes during embryogenesis and tumor progression. Hepatocyte growth factor (HGF), a protein isolated from serum of patients with liver failure, is a potent mitogen for hepatocytes and is thought to play a role in liver regeneration. Here we present structural and functional evidence that human SF and human HGF (and also the human lung fibroblast-derived mitogen) are identical proteins encoded by a single gene, since (i) no major difference could be found by protein sequencing, by cDNA analysis, and by immunological comparison and (ii) SF in fact acts as a hepatocyte growth factor--i.e., stimulates DNA synthesis of activity--i.e., dissociates and induces invasiveness of various epithelial cells. The human SF/HGF gene was localized to chromosome bands 7q11.2-21. These results have important consequences for further studies on the involvement of SF/HGF as a modulator of cellular growth and motility in embryonal, malignant, and regenerative processes.