Activation of Basic Fibroblast Growth Factor (bFGF) by Heparan Sulphate (HS)

Abstract

Fibroblast growth factors (FGFs) deliver their signals to cells by interacting with cellular receptors. There are two types of receptors for FGFs, namely heparan sulphate proteoglycans (HSPGs) and receptor tyrosine kinases (FGFRs). The functions of the HSPG receptors include: (i) the activation of FGFs which enables them to bind to the FGFRs with high-affinity; (ii) the extracellular storage of bFGF and hence its sequestration from the cell-surface tyrosine kinase receptors. bFGF is a normal product of mammary myoepithelial, but not epithelial, cells (Rudland et al., 1993). The rat mammary cells that are stimulated to proliferate by bFGF are stroma-derived fibroblasts and epithelium-derived intermediate cells of the terminal end buds and myoepithelial cells. These cell types are stimulated to proliferate as a consequence of their possessing receptors for bFGF while epithelial cells from normal mammary gland neither respond to bFGF nor possess detectable receptors for bFGF (Fernig et al., 1990, 1993). However, malignant mammary epithelial cells possess FGFRs, though not detectable HSPG receptors for bFGF, and they are responsive to exogenous bFGF (Fernig et al., 1993).