ROLE OF SCATTER FACTOR IN THE PATHOGENESIS OF AIDS-RELATED KAPOSI-SARCOMA

Kaposi sarcoma (KS) is a complex multicellular neoplasm that is common ly associated with AIDS. The pathogenesis of KS is not well understood . KS tumor cells grow poorly in vitro and require medium conditioned b y retrovirus-infected T lymphocytes. We observed that conditioned medi um (CM) from type II human T-cell leukemia virus (HTLV-II)-infected T cells (HTLV-II CM) induces conversion of endothelial cells (ECs) to a KS tumor cell-like phenotype. ECs grown in HTLV-II CM acquired a spind le-shaped morphology, the ability to express factor XIIIa and other KS cell markers, and a cytokine production profile similar to that of KS cells. We found that HTLV-II CM contains large quantities of scatter factor (SF), an angiogenic cytokine that stimulates cell motility. SF induced ECs to become spindle-shaped and express factor XIIIa. Moreove r, SF was found to be a mitogen for KS cells in vitro and was identifi ed within KS lesions in vivo. SF mRNA was present in KS cells in vitro , and antibodies against SF inhibited the growth of KS cells. The rece ptor for SF, the c-met protein, was expressed by ECs, dermal dendrocyt es, and KS tumor cells in vitro and in vivo. HTLV-II CM was highly ang iogenic in vivo, which was blocked by antibodies against SF. Based on these findings, we suggest that SF plays a role in the initiation and maintenance of KS lesions.