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。而且一些 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。此外，转移性 肿瘤变体产生促进其自身移动性的因子。我们计划 为了进一步鉴定这些肿瘤细胞引诱剂和运动促进剂， 并确定它们是否在转移性肿瘤中发挥作用， 过程几种趋化因子（例如，MCP-1和IL-8）已被 增强肿瘤免疫反应。由于树突状细胞（DC）， 最有效的抗原呈递细胞（APC），有助于肿瘤 我们刚刚完成了一项关于趋化因子对DC影响的研究。 许多C-C趋化因子（例如，MCP-1、MCP-2、MCP-3、MIP 1a和 RANTES）对人DC具有趋化性，表明它们可能 有助于动员这些强有力的APC。我们计划利用 通过研究对小鼠肿瘤的免疫反应， 用DC的最有效的化学引诱物转染。研究还 已经开始开发突变变体和肽类似物 趋化因子和它们的受体。这些实验只产生了 迄今为止的弱对手。一些消炎药 植物提取物可能含有天然的促炎抑制剂 化学引诱剂也在评估中。提取物中的一些成分 含有趋化因子抑制剂。最近， 启动了研究，以确定HIV-1包膜蛋白是否干扰 和趋化因子事实上，gp 120可以竞争性地抑制 MIP 1a和RANTES对人单核细胞的作用。进一步纯化和 需要进行表征研究，以确定 分子实体 HIV-1包膜中趋化因子拮抗剂的鉴定 proteins.

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, MIP1a 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 MIP1a and RANTES to human monocytes. Further purification and characterization studies are needed to identify the responsible molecular entities. AIDS TITLE: Identification of chemokine antagonists in HIV-1 envelope proteins.