Pyrrolidine dithiocarbamate prevents the induced expression of VCAM-1 in Kaposi's sarcoma 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.

Pyrrolidine dithiocarbamate prevents the induced expression of VCAM-1 in Kaposi's sarcoma cells (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 35:A2836 1994. Unique Identifier : AIDSLINE ICDB/95604521
Offermann MK; Medford RM; Shaw R; Emory University, Atlanta, GA 30322

Abstract: Kaposi's sarcoma (KS) is a neoplasm with multifocal vascular lesions that is seen in over 20% of HIV infected individuals. Evidence suggests that products of T-lymphocytes and monocytes are major contributors to the pathogenesis of KS. Biopsies of KS lesions demonstrate high levels of expression of the cellular adhesion molecules (CAM) VCAM-1 and ICAM-1, and higher levels of expression are associated with denser leukocyte infiltration. In cultured KS cells, both VCAM-1 and ICAM-1 are highly inducible by multiple agents, including double stranded RNA, IL-1 beta, TNF alpha, and LPS, and this increased expression leads to increased adhesion of leukocytes that express the counterreceptors. Without induction, cultured KS cells express no detectable VCAM-1 and low ICAM-1. This suggests that host factors such as cytokines, LPS, and viral infections are likely involved in the high levels of CAM expression observed in vivo. By gel shift analysis, CAM induction by multiple agents leads to NF-kappaB binding activity. Pyrrolidine dithiocarbamate (PDTC) blocks NF-kappaB activation by multiple agents, and this blocks the induced expression of VCAM-1 in KS cells. The ability of PDTC to completely block VCAM-1 expression by multiple agents suggests that this or a related agent might have a therapeutic role in the treatment of KS by preventing VCAM-1-mediated adhesion of lymphocytes and monocytes, cells strongly implicated in the pathogenesis of KS.

Keywords: Cell Adhesion Molecules/*METABOLISM/PHARMACOLOGY Human Intercellular Adhesion Molecule-1/*METABOLISM Interleukin-1/PHARMACOLOGY Lipopolysaccharides/PHARMACOLOGY NF-kappa B/METABOLISM Pyrrolidines/*PHARMACOLOGY Sarcoma, Kaposi's/*METABOLISM Thiocarbamates/*PHARMACOLOGY Tumor Necrosis Factor/PHARMACOLOGY ABSTRACT
950430
M9541137

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