Expression of functional tyrosine kinases on immortalized Kaposi's sarcomacells

Kaposi's sarcoma (KS) is the most frequent malignant lesion in patients wit h AIDS and is characterized by spindle cell proliferation, inflammatory cel l infiltration, angiogenesis, edema, and invasiveness. KS origin is still d ebated. The complex aspect of this disease is probably supported by multipl e concomitant pathogenetic factors, among which growth factors and their co gnate tyrosine kinase receptors are deeply involved. Here we have investiga ted the expression status and functional integrity of KDR and Met receptors , as well as of their ligands, in an immortalized KS cell line (KS-IMM). Th e MET and KDR genes encode the tyrosine kinase receptors for Hepatocyte Gro wth Factor (HGF) and Vascular Endothelial Growth Factor (VEGF) respectively . Both factors are pleiotropic cytokines controlling growth, survival, moti lity, invasive migration and differentiation of endothelial cells. We have found that KS-IMM cells, which retain most of the features of the parental tumor and can induce KS-like sarcomas when injected subcutaneously in nude mice, express the Met receptor, but not its ligand. The receptor, which is basally inactive, is functional, being tyrosine phosphorylated in response to ligand stimulation and mediating the expected HGF-dependent biological r esponses of motility, invasion and proliferation. Moreover, we report that KS-IMM cells coexpress VEGF and KDR and that KDR is constitutively tyrosine phosphorylated, possibly as a consequence of the establishment of an autoc rine loop. The receptor, however, maintains responsiveness to exogenously a dded ligand, by increasing the level of tyrosine phosphorylation and by res ponding in biological assays of motility, invasion and proliferation. Final ly, we have found that the two growth factors synergize in a motility assay . These data show that HGF and VEGF are growth factors active on KS-IMM cel ls. J. Cell. Physiol. 184:246-254, 2000. (C) 2000 Wiley-Liss, Inc.