Regulation of adhesion molecule expression in Kaposi's sarcoma cells.
Kaposi's sarcoma (KS) is a neoplasm with multifocal vascular lesions that is often seen in homosexual HIV-infected individuals. Infiltrates of leukocytes are characteristic components of KS lesions, and the products of leukocytes have been shown to enhance the proliferation of KS cells in vitro and most likely are crucial for the development of KS lesions in vivo. It is therefore likely that the expression of cellular adhesion molecules (CAM) is a critical determinant in the pathogenesis of KS by dictating the numbers and types of leukocytes that accumulate in areas predisposed to KS. We report that in the absence of inducers, KS cells in culture expressed low levels of ICAM-1 and undetectable VCAM-1 and E-selectin. ICAM-1, VCAM-1, and E-selectin were all induced by dsRNA (poly (I:C)), IL-1 beta, TNF-alpha, and LPS in KS cells. All of these agents increased NF-kappa B binding activity in nuclear extracts from KS cells. Neither human dermal fibroblasts nor human aortic smooth muscle cells had detectable VCAM-1 protein expression in response to conditions that led to high levels of VCAM-1 expression in KS cells. Although E-selectin expression was induced in KS cells, the peak cell surface protein levels were less than 25% the levels achieved on HUVEC or human dermal microvascular endothelial cells (HMEC). These low levels resembled the levels that were induced in HMEC immortalized with SV 40 large T Ag. These data indicate that multiple proinflammatory agents can induce NF-kappa B binding activity and can enhance ICAM-1, VCAM-1, and E-selectin expression in KS cells. The increased CAM expression enhances leukocyte binding to KS cells. Thus, the induction of CAM expression could be an early event in the development of KS by recruiting leukocytes into KS lesions, thereby providing factors that could potentiate the development of KS.
Yang
J
J
Winship Cancer Center, Atlanta, GA 30332.
Xu
Y
Y
Zhu
C
C
Hagan
M K
MK
Lawley
T
T
Offermann
M K
MK
D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D019040:E-Selectin; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000096:biosynthesis; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012514:Sarcoma, Kaposi / Q000276:immunology* / Q000473:pathology; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016328:NF-kappa B; D009363:Neoplasm Proteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1