ANTI-GROWTH FACTOR THERAPY IN KAPOSI'S SARCOMA IN AIDS

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Pulmonary Kaposi's Sarcoma (KS) is a potentially fatal form of KS and a complication of AIDS. KS cells grown in vitro respond to exogenous growth factors including platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) and are capable of expressing growth factor receptors. In the lung, the major source of growth factors is the alveolar macrophage that when activated, may release exaggerated amounts of growth factors providing competence (PDGF) and progression (insulin-like growth factor I, IGF-I) growth signals. We hypothesize that AM from patients with pulmonary KS release growth factors including PDGF, IFG-I, and possibly novel cytokines that stimulate KS cells to proliferate. To test this hypothesis, we will perform bronchoalveolar lavage (BAL) on 10 patients with pulmonary KS and compare AM release of growth factors to KS patients with skin involvement, asymptomatic HIV-infected individuals, and normals. AM supernatants will be evaluated in vitro for fibroblast and KS growth activity. To block growth factor ligand interaction with its receptor, we will evaluate supernatants with suramin, an anti-tumor agent capable of inhibiting binding of PDGF and IGF-I to their receptors. To further assess the state of AM activation, mRNA expression in AM for PDGF and IGF-I will be quantitated in all of the study groups. These experiments will contribute to understanding the paracrine mechanisms of KS tumor growth in the lung and a novel approach to therapy by blocking growth factor action.