CHEMOKINE TUMOR INTERACTIONS AND IDENTIFICATION OF CHEMOKINE ANTAGONISTS

趋化因子与上皮性肿瘤的相互作用 细胞表明，一些肿瘤细胞产生趋化因子，而一些表达 趋化因子的受体，并被其化学吸引。 此外，委员会认为， 某些肿瘤细胞类型被趋化因子刺激增殖。 此外，一些器官产生趋化因子， 转移性T细胞肿瘤变体。 净化研究表明 几种趋化因子，即RANTES和JE/MCP 1作为可能的贡献者 这些肿瘤细胞的转移性扩散。 另外还有按 转移性肿瘤变体产生促进其自身的因子 迁移率 我们计划进一步鉴定这些肿瘤细胞引诱剂， 运动促进剂，并确定它们是否在 转移过程。 几种趋化因子（例如，MCP-1和 IL-8）增强肿瘤免疫应答。 以来 树突状细胞（DC），最有效的抗原呈递细胞（APC）， 有助于肿瘤免疫，我们刚刚完成了一项研究， DC上的趋化因子 许多C-C趋化因子（例如，MCP-1， MCP-2、MCP-3、MIP 1 α和RANTES）对人DC具有趋化性， 这表明它们可能有助于动员这些潜在的 装甲运兵车 我们计划通过研究免疫系统来利用这些观察结果。 对转染了最有效的 DC的化学引诱物。 还开展了研究， 趋化因子的突变变体和肽类似物及其 受体。 这些实验只产生了弱拮抗剂， 约会 一些抗炎植物提取物可能 含有促炎化学引诱物的天然抑制剂， 正在评估。 芦荟提取物中的一些成分含有 趋化因子的抑制剂。 最近，我们开始研究， 确定HIV-1包膜蛋白是否干扰趋化因子。 事实上，gp 120可以竞争性地抑制MIP 1 α的结合， RANTES对人单核细胞的作用。 进一步纯化和表征 需要进行研究以确定负责的分子实体。

Our studies of the interactions of chemokines with epithelial tumor cells show that some tumor cells produce chemokines, while some express receptors for chemokines and are chemoattracted by them. Moreover, some tumor cell types are stimulated to proliferate by chemokines. Furthermore some organs produce chemotactic factors that attract metastatic T cell tumor variants. Purification studies have implicated several chemokines namely RANTES and JE/MCP1 as possible contributors to the metastatic spread of these tumor cells. In addition, a metastatic tumor variant produces factor(s) promoting their own mobility. We plan to further identify these tumor cell attractants and motility promoters and to establish whether they are playing a role in the metastatic process. Several of the chemokines (e.g., MCP-1 and IL-8) have been reported to enhance tumor immune responses. Since dendritic cells (DC), the most effective antigen presenting cell (APC), contribute to tumor immunity, we just completed a study of the effects of chemokines on DC. A number of the C-C chemokines (e.g., MCP-1, MCP-2, MCP-3, MIP1alpha and RANTES) are chemotactic for human DC, suggesting that they may contribute to the mobilization of these potent APC. We plan to exploit these observations by studying the immune response to murine tumors transfected with the most potent chemoattractants of DC. Studies also have been initiated to develop mutated variants and peptide analogues of chemokines and their receptors. These experiments have only generated weak antagonists to date. The possibility that some anti-inflammatory plant extracts may contain natural inhibitors of proinflammatory chemoattractants is also being evaluated. Some components in extracts of Aloe contain inhibitors of chemokines. Most recently we have initiated studies to establish whether HIV-1 envelope proteins interfere with chemokines. In fact, gp120 can competitively inhibit the binding of MIP1alpha and RANTES to human monocytes. Further purification and characterization studies are needed to identify the responsible molecular entities.