THE G3 DOMAIN OF VERSICAN ENHANCES CELL-PROLIFERATION VIA EPIDERMAL GROWTH FACTOR-LIKE MOTIFS

Versican is a member of the large aggregating chondroitin sulfate prot eoglycan family. We have expressed in NIH3T3 fibroblasts a recombinant versican mini-gene comprising the G1 and G3 domains and 15% of the CS domain. We observed that expression of the mini-versican gene stimula ted cell proliferation as determined by cell counting and cell cycle a nalysis. Addition of exogenous mini-versican protein to cultured cells produced the same result. The effects of the mini-versican were great ly reduced when the G3 domain was deleted. Expression of the G3 domain alone promotes cell proliferation, and addition of purified G3 gene p roducts to NIH3T3 fibroblasts and cultured chicken fibroblasts enhance s cell growth. Further, deletion of the epidermal growth factor (EGF)- like motifs in the versican G3 domain reduced the effects of the mini- versican on cell proliferation. In the presence of the purified mini-v ersican protein, antisense oligonucleotides to the EGF receptor inhibi ted proliferation of NIH3T3 fibroblasts, compared with control sense o ligonucleotides. Taken together, these results imply that versican enh ances cell proliferation, and this effect is mediated, at least in par t, by the action of versican EGF-like motifs on endogenous EGF recepto r.