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Expression of functional tyrosine kinases on immortalized Kaposi's sarcoma cells
Author(s) -
Montaldo Fabrizio,
Maffé Antonella,
Morini Monica,
Noonan Douglas,
Giordano Silvia,
Albini Adriana,
Prat Maria
Publication year - 2000
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/1097-4652(200008)184:2<246::aid-jcp13>3.0.co;2-o
Subject(s) - hepatocyte growth factor , receptor tyrosine kinase , autocrine signalling , biology , cancer research , tyrosine phosphorylation , tyrosine kinase , angiogenesis , motility , microbiology and biotechnology , receptor , platelet derived growth factor receptor , hepatocyte growth factor receptor , vascular endothelial growth factor , growth factor , paracrine signalling , phosphorylation , signal transduction , biochemistry , c met , vegf receptors
Kaposi's sarcoma (KS) is the most frequent malignant lesion in patients with AIDS and is characterized by spindle cell proliferation, inflammatory cell infiltration, angiogenesis, edema, and invasiveness. KS origin is still debated. The complex aspect of this disease is probably supported by multiple concomitant pathogenetic factors, among which growth factors and their cognate tyrosine kinase receptors are deeply involved. Here we have investigated 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). The MET and KDR genes encode the tyrosine kinase receptors for Hepatocyte Growth Factor (HGF) and Vascular Endothelial Growth Factor (VEGF) respectively. Both factors are pleiotropic cytokines controlling growth, survival, motility, 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 responses 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 autocrine loop. The receptor, however, maintains responsiveness to exogenously added ligand, by increasing the level of tyrosine phosphorylation and by responding in biological assays of motility, invasion and proliferation. Finally, 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 cells. J. Cell. Physiol. 184:246–254, 2000. © 2000 Wiley‐Liss, Inc.