Brayton J, Qing Z, Hart M N, VanGilder J C, Fabry Z
Department of Surgery, University of Iowa Hospital and Clinics, Iowa City 52242, USA.
J Neuroimmunol. 1998 Aug 14;89(1-2):104-12. doi: 10.1016/s0165-5728(98)00127-1.
Cultures of endothelial (En) cells derived from human brain microvessels were established in order to characterize adhesion molecule expression and to assay the adhesion properties of neoplastic cell lines to monolayers of En cells. Low constitutive expression of beta1 integrin (CD29), and ICAM-2 (CD102) was detected on human brain microvessel En cells. The beta1 chain of the VLA integrin family, ICAM-1, E-selectin (CD62E) and VCAM-1 (CD106) but not ICAM-2 and PECAM-1 (CD31) expression was upregulated by IL1-alpha, and TNF-alpha proinflammatory cytokines. High expression of PECAM-1 was found on non-activated human brain EN cells. In order to study the potential role of adhesion molecules in 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 pronounced 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 primary prostate carcinoma line (NDI) was significantly upregulated by TNF-alpha proinflammatory cytokine. Furthermore, the adhesion of ND1 was partly inhibited using anti-E-selectin and VCAM-1 monoclonal antibodies. There was no significant effect of anti-adhesion antibodies on the adhesion characteristics of the cerebral metastatic (DU145) cell line. Our data demonstrate that different mechanisms are involved in the adhesion of neoplastic cells to cerebral En cells and turn our attention to the importance of adhesion molecule expression in the formation of metastases.
为了表征黏附分子的表达并测定肿瘤细胞系对人脑微血管内皮（En）细胞单层的黏附特性，建立了源自人脑微血管的内皮（En）细胞培养体系。在人脑微血管En细胞上检测到β1整合素（CD29）和细胞间黏附分子-2（ICAM-2，CD102）的低组成性表达。VLA整合素家族的β1链、ICAM-1、E-选择素（CD62E）和血管细胞黏附分子-1（VCAM-1，CD106）的表达，但ICAM-2和血小板内皮细胞黏附分子-1（PECAM-1，CD31）的表达不受白细胞介素-1α和肿瘤坏死因子-α促炎细胞因子的上调。在未激活的人脑En细胞上发现PECAM-1的高表达。为了研究黏附分子在肿瘤细胞黏附中的潜在作用，选择了两种肿瘤细胞系。与原发性前列腺癌细胞系（ND1）的黏附相比，源自前列腺癌脑转移的细胞系（DU145）对人脑微血管En细胞单层的黏附不太明显。脑转移性肿瘤细胞系（DU145）的黏附不受内皮细胞与不同促炎细胞因子孵育的显著影响。原发性前列腺癌系（NDI）的黏附能力被肿瘤坏死因子-α促炎细胞因子显著上调。此外，使用抗E-选择素和VCAM-1单克隆抗体可部分抑制ND1的黏附。抗黏附抗体对脑转移性（DU145）细胞系的黏附特性没有显著影响。我们的数据表明，肿瘤细胞与人脑En细胞的黏附涉及不同机制，并使我们关注黏附分子表达在转移形成中的重要性。
