Department of Medicine, Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Prog Mol Biol Transl Sci. 2010;95:31-53. doi: 10.1016/B978-0-12-385071-3.00003-4.
Chemokines are a family of small and secreted proteins that play pleiotropic roles in inflammation-related pathological diseases, including cancer. Among the identified 50 human chemokines, chemokine (C-C motif) ligand 2 (CCL2) is of particular importance in cancer development since it serves as one of the key mediators of interactions between tumor and host cells. CCL2 is produced by cancer cells and multiple different host cells within the tumor microenvironment. CCL2 mediates tumorigenesis in many different cancer types. For example, CCL2 has been reported to promote prostate cancer cell proliferation, migration, invasion, and survival, via binding to its functional receptor CCR2. Furthermore, CCL2 induces the recruitment of macrophages and induces angiogenesis and matrix remodeling. Targeting CCL2 has been demonstrated as an effective therapeutic approach in preclinical prostate cancer models, and currently, neutralizing monoclonal antibody against CCL2 has entered into clinical trials in prostate cancer. In this chapter, targeting CCL2 in prostate cancer will be used as an example to show translation of laboratory findings from cancer molecular biology to the clinic.
趋化因子是一类小而分泌的蛋白质，在炎症相关的病理疾病（包括癌症）中发挥着多效性作用。在已鉴定的 50 个人类趋化因子中，趋化因子（C-C 基序）配体 2（CCL2）在癌症发展中尤为重要，因为它是肿瘤细胞与宿主细胞之间相互作用的关键介质之一。CCL2 由癌细胞和肿瘤微环境中的多种不同宿主细胞产生。CCL2 通过与其功能受体 CCR2 结合，介导多种不同癌症类型的肿瘤发生。例如，已有报道称 CCL2 通过与功能受体 CCR2 结合，促进前列腺癌细胞的增殖、迁移、侵袭和存活。此外，CCL2 诱导巨噬细胞的募集，并诱导血管生成和基质重塑。靶向 CCL2 已被证明是一种有效的治疗方法，在前列腺癌的临床前模型中，针对 CCL2 的中和单克隆抗体已进入前列腺癌的临床试验。在本章中，以靶向前列腺癌中的 CCL2 为例，展示从癌症分子生物学到临床的实验室发现的转化。
