National Cancer Institute, National Institutes of Health, Center for Cancer Research, Laboratory of Pathology, Bethesda, MD 20892-1500, USA.
Expert Opin Ther Targets. 2013 Jan;17(1):89-103. doi: 10.1517/14728222.2013.733699. Epub 2012 Oct 27.
CD47 is a ubiquitously expressed cell surface receptor that serves as a counter-receptor for SIRPα in recognition of self by the innate immune system. Independently, CD47 also functions as an important signaling receptor for regulating cell responses to stress.
We review the expression, molecular interactions, and pathophysiological functions of CD47 in the cardiovascular and immune systems. CD47 was first identified as a potential tumor marker, and we examine recent evidence that its dysregulation contributes to cancer progression and evasion of anti-tumor immunity. We further discuss therapeutic strategies for enhancing or inhibiting CD47 signaling and applications of such agents in preclinical models of ischemia and ischemia/reperfusion injuries, organ transplantation, pulmonary hypertension, radioprotection, and cancer.
Ongoing studies are revealing a central role of CD47 for conveying signals from the extracellular microenvironment that limit cell and tissue survival upon exposure to various types of stress. Based on this key function, therapeutics targeting CD47 or its ligands thrombospondin-1 and SIRPα could have broad applications spanning reconstructive surgery, engineering of tissues and biocompatible surfaces, vascular diseases, diabetes, organ transplantation, radiation injuries, inflammatory diseases, and cancer.
CD47 是一种广泛表达的细胞表面受体，作为先天免疫系统识别自身的 SIRPα 的受体。独立地，CD47 还作为调节细胞对压力反应的重要信号受体发挥作用。
我们回顾了 CD47 在心血管和免疫系统中的表达、分子相互作用和病理生理功能。CD47 最初被确定为一种潜在的肿瘤标志物，我们研究了最近的证据表明其失调有助于癌症进展和逃避抗肿瘤免疫。我们进一步讨论了增强或抑制 CD47 信号的治疗策略，以及这些药物在缺血和缺血/再灌注损伤、器官移植、肺动脉高压、放射防护和癌症的临床前模型中的应用。
正在进行的研究揭示了 CD47 在从细胞外微环境传递信号方面的核心作用，这些信号限制了细胞和组织在暴露于各种类型的应激时的存活。基于这一关键功能，针对 CD47 或其配体血小板反应蛋白-1 和 SIRPα 的治疗方法可能具有广泛的应用，涵盖重建手术、组织和生物相容表面的工程、血管疾病、糖尿病、器官移植、辐射损伤、炎症性疾病和癌症。
