CNRS, FRE 3481, Matrice Extracellulaire et Dynamique Cellulaire, Université de Reims Champagne-Ardenne, Faculté des Sciences, Reims, France.
Br J Pharmacol. 2012 Dec;167(7):1415-30. doi: 10.1111/j.1476-5381.2012.02099.x.
CD47 is a ubiquitous 50 kDa five-spanning membrane receptor that belongs to the immunoglobulin superfamily. This receptor, also known as integrin-associated protein, mediates cell-to-cell communication by ligation to transmembrane signal-regulatory proteins SIRPα and SIRPγ and interacts with integrins. CD47 is also implicated in cell-extracellular matrix interactions via ligation with thrombospondins. Furthermore, CD47 is involved in many and diverse cellular processes, including apoptosis, proliferation, adhesion and migration. It also plays a key role in many immune and cardiovascular responses. Thus, this multifaceted receptor might be a central actor in the tumour microenvironment. Solid tumours are composed of not only cancer cells that actively proliferate but also other cell types including immune cells and fibroblasts that make up the tumour microenvironment. Tumour cell proliferation is strongly sustained by continuous sprouting of new vessels, which also represents a gate for metastasis. Moreover, infiltration of inflammatory cells is observed in most neoplasms. Much evidence has accumulated indicating that infiltrating leukocytes promote cancer progression. Given its ubiquitous expression on all the different cell types that compose the tumour microenvironment, targeting CD47 could represent an original therapeutic strategy in the field of oncology. We present a current overview of the biological effects associated with CD47 on cancer cells and stromal cells.
CD47 是一种普遍存在的 50kDa 五跨膜受体，属于免疫球蛋白超家族。该受体也称为整合素相关蛋白，通过与跨膜信号调节蛋白 SIRPα 和 SIRPγ 的连接介导细胞间通讯，并与整合素相互作用。CD47 通过与血栓素结合也参与细胞-细胞外基质相互作用。此外，CD47 还参与许多不同的细胞过程，包括细胞凋亡、增殖、黏附和迁移。它还在许多免疫和心血管反应中发挥关键作用。因此，这种多方面的受体可能是肿瘤微环境中的核心角色。实体瘤不仅由积极增殖的癌细胞组成，还包括免疫细胞和成纤维细胞等组成肿瘤微环境的其他细胞类型。肿瘤细胞的增殖强烈依赖于新血管的持续发芽，这也是转移的一个门户。此外，大多数肿瘤中都观察到炎症细胞的浸润。大量证据表明，浸润的白细胞促进癌症的进展。鉴于 CD47 在构成肿瘤微环境的所有不同细胞类型上普遍表达，靶向 CD47 可能代表肿瘤学领域的一种原始治疗策略。我们目前概述了与癌症细胞和基质细胞上的 CD47 相关的生物学效应。
