A novel anti-angiogenic protein, apolipoprotein E3, inhibits angiogenesis by blocking the G1 to S transition of Kaposi's sarcoma-derived spindle cells (Meeting abstract).

Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

A novel anti-angiogenic protein, apolipoprotein E3, inhibits angiogenesis by blocking the G1 to S transition of Kaposi's sarcoma-derived spindle cells (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 36:A198 1995. Unique Identifier : AIDSLINE ICDB/95607978
Wang W; Sethi A; Vogel T; Browning PJ; Vanderbilt Univ., Nashville, TN 37232

Abstract: Acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS) and atherosclerosis are cytokine mediated diseases that share many common features. Both diseases are associated with a decrease in plasma high density lipoproteins (HDL) that contain an apolipoprotein termed apolipoprotein E3 (ApoE3). We demonstrated that Escherichia coli recombinant ApoE3 inhibits vascular endothelial cell growth and migration in vitro. From these studies we hypothesized that ApoE3 may be anti-angiogenic. We found that ApoE3 inhibits AIDS-KS cell proliferation in vitro, and vascular permeability and angiogenesis induced by these cells in vivo. The objective of these studies was to determine how ApoE3 inhibits AIDS-KS cell growth. We observed that the inhibitory effect was not toxic, but cytostatic. AIDS-KS cells were arrested in G0 by growth to high cell density followed by serum starvation for 72 hr. When these cells were released from G0 by plating sparsely in serum-containing medium, they entered S phase (DNA synthesis) between 14 to 18 hr. When ApoE3 was added to the sparsely plated cells we observed a block in the transition form G1 to S. These findings suggest a novel mechanism of action of this anti-angiogenic molecule. Further mechanistic studies regarding this cell cycle regulator of angiogenesis will be discussed.

Keywords: Acquired Immunodeficiency Syndrome/COMPLICATIONS/*PATHOLOGY Apolipoproteins E/*PHARMACOLOGY Capillary Permeability/DRUG EFFECTS G1 Phase/*DRUG EFFECTS Human Neovascularization, Pathologic/*PREVENTION & CONTROL S Phase/*DRUG EFFECTS Sarcoma, Kaposi's/*PATHOLOGY/THERAPY Tumor Cells, Cultured ABSTRACT
950630
M9561163

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