Regulation of adhesion molecule expression in Kaposi's sarcoma cells.
Regulation of adhesion molecule expression in Kaposi's sarcoma cells.
复制标题
卡波西肉瘤细胞中粘附分子表达的调节。
作者：
Jing Yang;Yuelin Xu;Cheng Zhu;M. Hagan;T. Lawley;M. Offermann
卡波西肉瘤 (KS) 是一种多灶性血管病变的肿瘤，常见于同性恋 HIV 感染者。白细胞浸润是 KS 病变的特征性成分，白细胞产物已被证明可在体外增强 KS 细胞的增殖，并且很可能对体内 KS 病变的发展至关重要。因此，细胞粘附分子 (CAM) 的表达可能是 KS 发病机制的关键决定因素，它决定了易患 KS 区域的白细胞的数量和类型。我们报告，在没有诱导剂的情况下，培养中的 KS 细胞表达低水平的 ICAM-1 和不可检测的 VCAM-1 和 E-选择素。 ICAM-1、VCAM-1 和 E-选择素均由 KS 细胞中的 dsRNA (poly (I:C))、IL-1 beta、TNF-α 和 LPS 诱导。所有这些药物都增加了 KS 细胞核提取物中 NF-κ B 的结合活性。在导致 KS 细胞中高水平 VCAM-1 表达的条件下，人真皮成纤维细胞和人主动脉平滑肌细胞均未检测到 VCAM-1 蛋白表达。尽管 KS 细胞中诱导了 E-选择素表达，但细胞表面蛋白峰值水平低于 HUVEC 或人真皮微血管内皮细胞 (HMEC) 上达到的水平的 25%。这些低水平类似于用 SV 40 大 T Ag 永生化的 HMEC 中诱导的水平。这些数据表明多种促炎剂可以诱导 NF-κ B 结合活性，并可以增强 KS 细胞中 ICAM-1、VCAM-1 和 E-选择素的表达。 CAM 表达增加可增强白细胞与 KS 细胞的结合。因此，通过将白细胞募集到 KS 病变中，CAM 表达的诱导可能是 KS 发展的早期事件，从而提供可以增强 KS 发展的因子。
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.