Exogenous fibroblast growth factor-2 induces a transformed phenotype in vascular kaposi's sarcoma-like cells

摘要

Vascular TTB cells derive from murine Kaposi’s arcoina-like dermal lesions and share several pheno-typic features with AIDS-associated KS spindle cells.We have recently reported that fibroblast growthfactor-2(FGF-2) promotes dramatic cytoskeletal andmorphological alterations in TTB cells, concomitantwith the induction of an autocrine loop for hepatocytegrowth factor and a relocalization of the urokinasereceptor.Since all these alterations are hallmarks ofcell transformation. we attempted to verify whetherFGF-2 induces a transformed phenotype in TTB cells.Our results show that FGF-2-treated TTB cells acquirethe ability to grow under anchorage-independent con-ditions. In addition, FGF-2 markedly reduced the 1ev-els of thrombospondin-1, an antiangiogenic and tumorsuppressor protein, in TTB cells. Therefore, FGF-2 in-duces KS-like spindle cells to acquire properties char-acteristic of transformed cells. This suggests thatFGF-2 plays a pathogenetic role in KS not only bypromoting angiogenesis, but also by conferring atransformed phenotype upon KS cells. In light of pre-vious reports on Tat-induced release of FGF-2 into theextracellular space, our findings may provide an addi-tional mechanism for the observed synergism betweenTat and FGF-2 in the pathogenesis of KS.