Arya Manit, Ahmed Hashim, Silhi Nitika, Williamson Magali, Patel Hiten R H
University College London, London, UK.
Tumour Biol. 2007;28(3):123-31. doi: 10.1159/000102979. Epub 2007 May 18.
Chemokines are small, secreted proteins and are now the largest known cytokine family. They mediate their effects through a family of G-protein-coupled receptors and were initially recognized for their ability to act as chemo-attractants and activators of specific types of leucocytes in a variety of immune and inflammatory responses. However, during the past 5 years there has been a chemokine revolution in cancer and all scientists and clinicians in oncology-related fields are now aware of their crucial role at all stages of neoplastic transformation and progression. The most important chemokine ligand-receptor interaction is that of the CXCL12 (stromal cell-derived factor-1, SDF-1) ligand with its exclusive receptor CXCR4; this interaction has a pivotal role in the directional migration of cancer cells during the metastatic process. This has been demonstrated by in vitro and in vivo experiments in addition to retrospective clinical studies. These findings have exciting implications in the field of cancer therapeutics, with several small molecule CXCR4 antagonists having been developed, which may provide clinical benefit in the therapy of cancer metastasis. Interestingly, it is likely that the effect of the anti-HER2 antibody [trastuzumab (Herceptin] in breast cancer involves downregulation of the CXCR4 receptor. Unfortunately, a major problem is that chemokine receptors are expressed in other cells within the body, particularly those of the immune system and it is not clear what effects long-term CXCR4 antagonism could have on innate and adaptive immunity. However, there is little doubt that the great strides made in elucidating the complex relationship between chemokines and their role in cancer will soon translate into significant survival benefits for patients.
趋化因子是一类小分子分泌蛋白，是目前已知最大的细胞因子家族。它们通过一类G蛋白偶联受体介导其作用，最初因其在多种免疫和炎症反应中作为特定类型白细胞的化学吸引剂和激活剂的能力而被认识。然而，在过去5年里，癌症领域发生了一场趋化因子革命，所有肿瘤学相关领域的科学家和临床医生现在都意识到它们在肿瘤转化和进展的各个阶段都起着关键作用。最重要的趋化因子配体-受体相互作用是CXCL12（基质细胞衍生因子-1，SDF-1）配体与其唯一受体CXCR4之间的相互作用；这种相互作用在转移过程中癌细胞的定向迁移中起关键作用。体外和体内实验以及回顾性临床研究都证明了这一点。这些发现对癌症治疗领域具有令人兴奋的意义，已经开发出几种小分子CXCR4拮抗剂，它们可能在癌症转移治疗中提供临床益处。有趣的是，抗HER2抗体[曲妥珠单抗（赫赛汀）]在乳腺癌中的作用可能涉及CXCR4受体的下调。不幸的是，一个主要问题是趋化因子受体在体内的其他细胞中表达，特别是免疫系统的细胞，目前尚不清楚长期CXCR4拮抗作用对先天免疫和适应性免疫会有什么影响。然而，毫无疑问，在阐明趋化因子之间的复杂关系及其在癌症中的作用方面取得的巨大进展很快将转化为患者显著的生存益处。
