Basic fibroblast growth factor modifies the interactions between endothelial cells/fibronectin: Implications for progression of AIDS- associated Kaposi's sarcoma

Kaposi's sarcoma (KS) is an angioproliferative disease frequently arising in HIV-1 infected individuals (AIDS-KS). Previous studies indicated that cells derived from AIDS-KS lesions (AIDS-KS cells) produce the angiogenic basic fibroblast growth factor (bFGF) and release it in a biologically active form. Here we show that this extracellular bFGF increases in endothelial cells the expression of fibronectin (FN)-degrading proteases, such as stromelysin-1, stromelysin-3 and collagenase IV, and of the FN- binding integrin α5β1. Consequently, bFGF produced by AIDS-KS cells improves the capability of endothelial cells to migrate toward FN digested and cleaved from blood vessel basement membrane and perivascular stroma by proteases. These results suggest a mechanism for two phenomena that characterize AIDS-KS lesions and that are fundamental for its progression: the invasivity of endothelial cells and the abnormal angiogenesis.