INFLUENCE OF ADHESION MOLECULE EXPRESSION BY HUMAN BRAIN MICROVESSEL ENDOTHELIUM ON CANCER CELL-ADHESION

Cultures of endothelial (En) cells derived from human brain microvesse ls were established in order to characterize adhesion molecule express ion and to assay the adhesion properties of neoplastic cell lines to m onolayers of En cells. Low constitutive expression of beta 1 integrin (CD29), and ICAM-2 (CD102) was detected on human brain microvessel En cells. The beta 1 chain of the VLA integrin family, ICAM-1, E-selectin (CD62E) and VCAM-1 (CD106) but not ICAM-2 and PECAM-1 (CD31) expressi on was upregulated by IL1-alpha, and TNF-alpha proinflammatory cytokin es. High expression of PECAM-1 was found on non-activated human brain EN cells. In order to study the potential role of adhesion molecules i n neoplastic cell adhesion two tumor cell lines were chosen. Adhesion of a cell line (DU145) derived from a cerebral metastasis of prostate carcinoma to human brain microvessel En cell monolayers was less prono unced compared to adhesion of a primary prostate carcinoma cell line ( ND1). Adhesion of cerebral metastatic neoplastic cell line (DU145) was not significantly influenced by incubation of endothelial cells with different proinflammatory cytokines. The adhesion capability of primar y prostate carcinoma line (ND1) was significantly upregulated by TNF-a lpha proinflammatory cytokine. Furthermore, the adhesion of ND1 was pa rtly inhibited using anti-E-selectin and VCAM-1 monoclonal antibodies. There was no significant effect of anti-adhesion antibodies on the ad hesion characteristics of the cerebral metastatic (DU145) cell line. O ur data demonstrate that different mechanisms are involved in the adhe sion of neoplastic cells to cerebral En cells and turn our attention t o the importance of adhesion molecule expression in the formation of m etastases. (C) 1998 Elsevier Science B.V. All rights reserved.