Fulton Amy M
University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA.
Curr Oncol Rep. 2009 Mar;11(2):125-31. doi: 10.1007/s11912-009-0019-1.
Chemokines comprise a superfamily of at least 46 cytokines that were initially described based on their ability to bind to 18 to 22 G protein-coupled receptors to induce the directed migration of leukocytes to sites of inflammation or injury. In addition to mediating cellular migration, chemokine/chemokine receptor pairs have been shown to affect many cellular functions, including survival, adhesion, invasion, and proliferation, and to regulate circulating chemokine levels. Most malignancies also express one or more chemokine receptors. Early studies established a role for CXCR4 and CXCR7 in mediating breast cancer metastasis, but other chemokine receptors, including CXCR3, now are implicated in several malignancies as biomarkers of tumor behavior as well as potential therapeutic targets. This review summarizes our current understanding regarding the contribution of CXCR4 and CXCR3 to tumor behavior and how receptor expression is regulated, transduces intracellular signals, and contributes at the molecular level to tumor behavior. It also describes recent therapeutic approaches that target these receptors or their ligands.
趋化因子构成了一个至少由46种细胞因子组成的超家族，最初是根据它们与18至22种G蛋白偶联受体结合以诱导白细胞向炎症或损伤部位定向迁移的能力来描述的。除了介导细胞迁移外，趋化因子/趋化因子受体对还被证明可影响许多细胞功能，包括存活、黏附、侵袭和增殖，并调节循环趋化因子水平。大多数恶性肿瘤也表达一种或多种趋化因子受体。早期研究确定了CXCR4和CXCR7在介导乳腺癌转移中的作用，但其他趋化因子受体，包括CXCR3，现在也作为肿瘤行为的生物标志物以及潜在的治疗靶点与多种恶性肿瘤有关。本综述总结了我们目前对CXCR4和CXCR3对肿瘤行为的贡献以及受体表达如何被调控、转导细胞内信号并在分子水平上对肿瘤行为产生影响的理解。它还描述了针对这些受体或其配体的最新治疗方法。
