CXCR4在癌症中的复杂作用。
The intricate role of CXCR4 in cancer.
作者信息
Chatterjee Samit, Behnam Azad Babak, Nimmagadda Sridhar
机构信息
Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland, USA.
Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland, USA.
出版信息
Adv Cancer Res. 2014;124:31-82. doi: 10.1016/B978-0-12-411638-2.00002-1.
Chemokines mediate numerous physiological and pathological processes related primarily to cell homing and migration. The chemokine CXCL12, also known as stromal cell-derived factor-1, binds the G-protein-coupled receptor CXCR4, which, through multiple divergent pathways, leads to chemotaxis, enhanced intracellular calcium, cell adhesion, survival, proliferation, and gene transcription. CXCR4, initially discovered for its involvement in HIV entry and leukocytes trafficking, is overexpressed in more than 23 human cancers. Cancer cell CXCR4 overexpression contributes to tumor growth, invasion, angiogenesis, metastasis, relapse, and therapeutic resistance. CXCR4 antagonism has been shown to disrupt tumor-stromal interactions, sensitize cancer cells to cytotoxic drugs, and reduce tumor growth and metastatic burden. As such, CXCR4 is a target not only for therapeutic intervention but also for noninvasive monitoring of disease progression and therapeutic guidance. This review provides a comprehensive overview of the biological involvement of CXCR4 in human cancers, the current status of CXCR4-based therapeutic approaches, as well as recent advances in noninvasive imaging of CXCR4 expression.
趋化因子介导众多主要与细胞归巢和迁移相关的生理和病理过程。趋化因子CXCL12，也称为基质细胞衍生因子-1，与G蛋白偶联受体CXCR4结合，通过多种不同途径导致趋化作用、细胞内钙增加、细胞黏附、存活、增殖和基因转录。CXCR4最初因其参与HIV进入和白细胞运输而被发现，在超过23种人类癌症中过度表达。癌细胞CXCR4的过度表达促进肿瘤生长、侵袭、血管生成、转移、复发和治疗抗性。已证明CXCR4拮抗作用可破坏肿瘤-基质相互作用，使癌细胞对细胞毒性药物敏感，并减少肿瘤生长和转移负担。因此，CXCR4不仅是治疗干预的靶点，也是疾病进展的无创监测和治疗指导的靶点。本综述全面概述了CXCR4在人类癌症中的生物学作用、基于CXCR4的治疗方法的现状以及CXCR4表达的无创成像的最新进展。
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