Wang Zhidong, Sun Jian, Feng Yeqian, Tian Xiaocai, Wang Bin, Zhou Yong
Oncology Department, Eighth Hospital of Changsha, No. 22, Xingsha Avenue, Changsha, 410100, Hunan Province, China.
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, 510060, Guangdong Province, China.
Tumour Biol. 2016 Jul;37(7):8515-28. doi: 10.1007/s13277-016-5016-z. Epub 2016 Apr 14.
Although the great progress has been made in diagnosis and therapeutic in lung cancer, it induces the most cancer death worldwide in both males and females. Chemokines, which have chemotactic abilities, contain up to 50 family members. By binding to G protein-coupled receptors (GPCR), holding seven-transmembrane domain, they function in immune cell trafficking and regulation of cell proliferation, differentiation, activation, and migration, homing under both physiologic and pathologic conditions. The alpha-chemokine receptor CXCR4 for the alpha-chemokine stromal cell-derived-factor-1 (SDF-1) is most widely expressed by tumors. In addition to human tissues of the bone marrow, liver, adrenal glands, and brain, the CXC chemokine SDF-1 or CXCL12 is also highly expressed in lung cancer tissues and is associated with lung metastasis. Lung cancer cells have the capabilities to utilize and manipulate the CXCL12/CXCR system to benefit growth and distant spread. CXCL12/CXCR4 axis is a major culprit for lung cancer and has a crucial role in lung cancer initiation and progression by activating cancer stem cell. This review provides an evaluation of CXCL12/CXCR4 as the potential therapeutic target for lung cancers; it also focuses on the synergistic effects of inhibition of CXCL12/CXCR4 axis and immunotherapy as well as chemotherapy. Together, CXCL12/CXCR4 axis can be a potential therapeutic target for lung cancers and has additive effects with immunotherapy.
尽管在肺癌的诊断和治疗方面已经取得了巨大进展，但它在全球范围内导致男性和女性癌症死亡人数最多。趋化因子具有趋化能力，包含多达50个家族成员。通过与具有七个跨膜结构域的G蛋白偶联受体（GPCR）结合，它们在免疫细胞运输以及细胞增殖、分化、激活和迁移的调节中发挥作用，并在生理和病理条件下归巢。肿瘤中最广泛表达的是针对α趋化因子基质细胞衍生因子-1（SDF-1）的α趋化因子受体CXCR4。除了骨髓、肝脏、肾上腺和大脑的人体组织外，CXC趋化因子SDF-1或CXCL12在肺癌组织中也高度表达，并与肺转移有关。肺癌细胞有能力利用和操纵CXCL12/CXCR系统以促进生长和远处扩散。CXCL12/CXCR4轴是肺癌的主要罪魁祸首，通过激活癌症干细胞在肺癌的发生和发展中起关键作用。本综述评估了CXCL12/CXCR4作为肺癌潜在治疗靶点的情况；还重点关注了抑制CXCL12/CXCR4轴与免疫疗法以及化疗的协同作用。总之，CXCL12/CXCR4轴可能是肺癌的潜在治疗靶点，并且与免疫疗法具有相加作用。
