title: Kaposi's sarcoma cells of different etiologic origins respond to HIV-Tat through the Flk-1/KDR (VEGFR-2): relevance in AIDS-KS pathology.
abstract: Kaposi's sarcoma (KS) is an hyperplastic lesion whose main histological features are typical spindle shaped cells with a mixed endothelial-mesenchymal-macrophage phenotype, an intense vascularization and an inflammatory infiltrate. The etiology of KS appears to be linked to activation of a latent HHV8 infection. Sporadic and iatrogenic KS are slow progressing lesions that can undergo spontaneous regression. In contrast, KS, which is frequently associated with HIV infection, is found in a highly aggressive form in AIDS patients. The HIV-1 Tat has been shown to activate the VEGF receptor KDR in endothelial and KS spindle cells, suggesting this HIV protein could contribute to KS pathogenesis. We used primary 'reactive' KS cell culture from sporadic and epidemic KS, and an immortal KS-line (KS-Imm) isolated in our laboratory from a iatrogenic KS lesion, to verify if Tat-induced cell signaling is able to mediate cellular responses. We demonstrate that KS cells migrated in response to Tat and that VEGF is able to compete with the Tat chemotactic activity towards these cells. A function-blocking anti-KDR antibody was able to abrogate both VEGF and Tat-induced KS chemotactic response, indicating a direct involvement of this receptor. Our data show that HIV-Tat can also activate KS cells derived from sporadic or iatrogenic lesions, suggesting that in AIDS patients Tat could cooperate with VEGF in activation of KDS on KS precursor spindle and endothelial cells, and contribute to the aggressiveness of AIDS-KS lesions.
authors.affiliation: Molecular Biology Laboratory, Tumor Progression Section, Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, Genoa, 16132, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Morini
authors.forename: R
authors.initials: R
authors.lastname: Benelli
authors.forename: D
authors.initials: D
authors.lastname: Giunciuglio
authors.forename: S
authors.initials: S
authors.lastname: Carlone
authors.forename: G
authors.initials: G
authors.lastname: Arena
authors.forename: D M
authors.initials: DM
authors.lastname: Noonan
authors.forename: A
authors.initials: A
authors.lastname: Albini
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D000906:Antibodies / Q000494:pharmacology; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D015696:Gene Products, tat / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008222:Lymphokines / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor; D012514:Sarcoma, Kaposi / Q000150:complications / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D000906:Antibodies; D002630:Chemotactic Factors; D016228:Endothelial Growth Factors; D015696:Gene Products, tat; D008222:Lymphokines; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D019000:Phosphotyrosine; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor