DIFFERENCES IN BINDING TO THE SOLID SUBSTRATUM AND EXTRACELLULAR-MATRIX MAY EXPLAIN ISOFORM-SPECIFIC PARACRINE EFFECTS OF PLATELET-DERIVED GROWTH-FACTOR

We have studied the paracrine response of fibroblasts to the two homod imeric isoforms of platelet-derived growth factor (PDGF-AA and -BB). C HO-cells stably transfected with a B-chain cDNA expression vector (CHO -PDGF-B cells), were found to elicit a marked paracrine response when seeded at clonal density on preformed monolayers of human or murine fi broblasts; no such response was elicited by CHO-PDGF-A cells. Immunofl uorescence microscopy of CHO-PDGF-B cell cultures showed the presence of a pericellular deposit of material reacting with antibodies against PDGF-BB; no corresponding PDGF-AA immunoreactive material was found i n the CKO-PDGF-A cultures. The pericellular material, deposited by CHO -PDGF-B cells, was shown to have a growth promoting effect on target c ells. Furthermore, we could show that I-125-PDGF-BB binds more efficie ntly than I-125-PDGF-AA to extracellular matrix prepared from foreskin fibroblast cultures, as well as to defined extracellular matrix compo nents (fibronectin, laminin and collagen III). The results reveal a ma rked difference in the paracrine activity of PDGF-AA and PDGF-BB; the latter has a strong local growth enhancing effect, that is most likely to be ascribed to its association with components of the extracellula r matrix.