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Singh, A.B. et al.

Membrane-associated HB- EGF modulates HGF-induced cellular responses in MDCK cells.

In MDCK cells, hepatocyte growth factor/scatter factor ( HGF/SF) induces epithelial cell dissociation, scattering, migration, growth and formation of branched tubular structures. By contrast, these cells neither scatter nor form tubular structures in response to the epidermal growth factor ( EGF) family of growth factors. Heparin-binding EGF-like growth factor (HB- EGF) is a member of the EGF family of growth factors and is synthesized as a membrane-associated precursor molecule (proHB- EGF). ProHB- EGF is proteolytically cleaved to release a soluble ligand (sHB- EGF) that activates the EGF receptor. Although recent studies suggest possible physiological functions, the role of proHB- EGF remains largely undefined. Using MDCK cells stably expressing proHB- EGF, a noncleavable deletion mutant of proHB- EGF or soluble HB- EGF, we show that epithelial cell functions differ depending on the form of HB- EGF being expressed. Expression of noncleavable membrane-anchored HB- EGF promoted cell-matrix and cell-cell interactions and decreased cell migration, HGF/SF-induced cell scattering and formation of tubular structures. By contrast, expression of soluble HB- EGF induced increased cell migration, decreased cell-matrix and cell-cell interactions and promoted the development of long unbranched tubular structures in response to HGF/SF. These findings suggest that HB- EGF can not only modulate HGF/SF- induced cellular responses in MDCK cells but also that membrane- bound HB- EGF and soluble HB- EGF give rise to distinctly different effects on cell-cell and cell-extracellular matrix interactions.[1]

References

Membrane-associated HB-EGF modulates HGF-induced cellular responses in MDCK cells. Singh, A.B., Tsukada, T., Zent, R., Harris, R.C. J. Cell. Sci. (2004) [Pubmed]

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