An autocrine model for cell- and matrix-associated fibroblast growth factor

While the prototypic fibroblast growth factors (FGFs) are known to have important roles in the stimulation of cell proliferation and angiogenesis, their lack of a conventional secretory signal peptide sequence has presented a challenge to our understanding of the mechanisms by which they are released from cells and subsequently engaged at cell-membrane-localized receptors. The autocrine and paracrine function of polypeptide growth factors has frequently involved the delivery of a large, transmembrane precursor molecule to the cell surface and its subsequent proteolytic release. Through the use of chimeric growth factors, and enhanced proteolytic release of cell-associated populations of growth factor precursors, it has been established that cell-associated growth factor populations can exhibit autocrine and paracrine activity. This commentary will draw upon the potential role of cell- and matrix-associated FGF populations to develop a model for the release of prototypic FGFs from low-affinity sites on the cell surface, or from extracellular matrix, to high-affinity, cellular receptors. It is proposed that cell- and matrix-associated FGF may exhibit autocrine function and provide the capacity to be regulated in a variety of normal and transformed cell systems. It is also proposed that growth factor delivery mechanisms involving cell- and matrix-associated ligand populations represent a specialized form of regulated delivery. This specialized delivery mechanism may confer autocrine advantages upon a variety of growth factor family gene products.