Angiogenic properties of human immunodeficiency virus type 1 Tat protein.
Extracellular human immunodeficiency virus type 1 (HIV-1) Tat protein promotes growth of spindle cells derived from AIDS-associated Kaposi sarcoma (AIDS-KS), an angioproliferative disease very frequent in HIV-1-infected individuals. Normal vascular cells, progenitors of AIDS-KS cells, proliferate in response to Tat after exposure to inflammatory cytokines, whose levels are augmented in HIV-1-infected individuals and in KS lesions. Here we show that Tat also promotes AIDS-KS and normal vascular cells to migrate and to degrade the basement membrane and stimulates endothelial cell morphogenesis on a matrix substrate. These effects are obtained at picomolar concentrations of exogenous Tat and are promoted by the treatment of the cells with the same inflammatory cytokines stimulating expression of the receptors for Tat, the integrins alpha 5 beta 1 and alpha v beta 3. Thus, under specific circumstances, Tat has angiogenic properties. As Tat and its receptors are present in AIDS-KS lesions, these data may explain some of the mechanisms by which Tat can induce angiogenesis and cooperate in the development of AIDS-KS.
Albini
A
A
Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Barillari
G
G
Benelli
R
R
Gallo
R C
RC
Ensoli
B
B
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D001012:Aorta, Abdominal / Q000166:cytology / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes; D002455:Cell Division / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D015696:Gene Products, tat / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D015458:Leukemia, T-Cell; D008233:Lymphotoxin-alpha / Q000494:pharmacology; D009024:Morphogenesis / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D009389:Neovascularization, Pathologic; D012514:Sarcoma, Kaposi / Q000209:etiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins; D054322:tat Gene Products, Human Immunodeficiency Virus
D017077:Culture Media, Conditioned; D016207:Cytokines; D015696:Gene Products, tat; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D054322:tat Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor