Shim Hyunsuk, Oishi Shinya, Fujii Nobutaka
Department of Radiology, Emory University, Atlanta, GA 30322, USA.
Semin Cancer Biol. 2009 Apr;19(2):123-34. doi: 10.1016/j.semcancer.2008.11.004. Epub 2008 Nov 25.
Chemokines (chemotactic cytokines) are a family of proteins associated with the trafficking and activation of leukocytes and other cell types in immune surveillance and inflammatory response. Besides their roles in the immune system, they play pleiotropic roles in tumor initiation, promotion, and progression. Chemokines can be classified into four subfamilies of chemokines, CXC, CC, C, or CX3C, based on their number and spacing of conserved cysteine residues near the N-terminus. This CXC subfamily can be further subclassified into two groups, depending on the presence or absence of a tripeptide motif glutamic acid-leucine-arginine (ELR) in the N-terminal domain. ELR(-)CXCL12, which binds to CXCR4 has been frequently implicated in various cancers. Over the past several years, studies have increasingly shown that the CXCR4/CXCL12 axis plays critical roles in tumor progression, such as invasion, angiogenesis, survival, homing to metastatic sites. This review focuses on involvement of CXCR4/CXCL12 interaction in neuroectodermal cancers and their therapeutic potentials. As an attractive therapeutic target of CXCR4/CXCL12 axis for cancer chemotherapy, development history and application of CXCR4 antagonists are described.
趋化因子（趋化性细胞因子）是一类蛋白质，在免疫监视和炎症反应中与白细胞及其他细胞类型的运输和激活相关。除了在免疫系统中的作用外，它们在肿瘤的起始、促进和进展过程中发挥着多效性作用。趋化因子可根据其N端附近保守半胱氨酸残基的数量和间距分为四个亚家族：CXC、CC、C或CX3C。根据N端结构域中是否存在三肽基序谷氨酸 - 亮氨酸 - 精氨酸（ELR），CXC亚家族可进一步细分为两组。与CXCR4结合的ELR（ - ）CXCL12常与多种癌症相关。在过去几年中，越来越多的研究表明，CXCR4/CXCL12轴在肿瘤进展中发挥关键作用，如侵袭、血管生成、存活、归巢至转移部位。本综述重点关注CXCR4/CXCL12相互作用在神经外胚层肿瘤中的作用及其治疗潜力。作为癌症化疗中CXCR4/CXCL12轴的一个有吸引力的治疗靶点，描述了CXCR4拮抗剂的开发历史和应用。
