HEPATOCYTE GROWTH-FACTOR ENABLES ENHANCED INTEGRIN-CYTOSKELETON LINKAGE BY AFFECTING INTEGRIN EXPRESSION IN SUBCONFLUENT EPITHELIAL-CELLS

Hepatocyte growth factor (HGF) exerts mitogenic and motogenic effects in different cell types. In the epithelial cell line mHepR1 we found t hat HGF induced pronounced alterations in cell morphology and promoted cell adhesion and spreading. To analyze the mechanisms how HGF affect s these integrin mediated functions we studied the physical linkage of integrins with the cytoskeleton, First we found that HGF increased th e expression of different integrin subunits in subconfluent cells and influenced the distribution of integrins on the cell surface. To addre ss the physical association of integrins with the cytoskeleton we anal yzed Triton X-100-extracted cell fractions using flow cytometry. Here we show that cultivation of the cells with HGF for 24 h prior to integ rin cross-linking significantly enhanced the cytoskeletal anchorage of integrins. To further find out whether HGF directly induces an integr in-cytoskeleton link without subsequent cross-linking we added HGF to suspended cells but failed to detect cytoskeletally immobilized integr ins in the detergent-insoluble cell fraction which could be related to the absence of a calcium response induced by HGF. Overall, the result s indicate that HGF promotes the physical linkage of integrins to the cytoskeleton which requires additional stimulation of integrins.