Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Int J Mol Sci. 2018 Dec 30;20(1):124. doi: 10.3390/ijms20010124.
Neuroimmune semaphorin 4A (Sema4A), a member of semaphorin family of transmembrane and secreted proteins, is an important regulator of neuronal and immune functions. In the nervous system, Sema4A primarily regulates the functional activity of neurons serving as an axon guidance molecule. In the immune system, Sema4A regulates immune cell activation and function, instructing a fine tuning of the immune response. Recent studies have shown a dysregulation of Sema4A expression in several types of cancer such as hepatocellular carcinoma, colorectal, and breast cancers. Cancers have been associated with abnormal angiogenesis. The function of Sema4A in angiogenesis and cancer is not defined. Recent studies have demonstrated Sema4A expression and function in endothelial cells. However, the results of these studies are controversial as they report either pro- or anti-angiogenic Sema4A effects depending on the experimental settings. In this mini-review, we discuss these findings as well as our data on Sema4A regulation of inflammation and angiogenesis, which both are important pathologic processes underlining tumorigenesis and tumor metastasis. Understanding the role of Sema4A in those processes may guide the development of improved therapeutic treatments for cancer.
神经免疫信号素 4A（Sema4A）是信号素家族跨膜和分泌蛋白的成员，是神经元和免疫功能的重要调节剂。在神经系统中，Sema4A 主要通过作为轴突导向分子来调节神经元的功能活性。在免疫系统中，Sema4A 调节免疫细胞的激活和功能，指导免疫反应的精细调节。最近的研究表明，几种类型的癌症（如肝细胞癌、结直肠癌和乳腺癌）中 Sema4A 的表达失调。癌症与异常血管生成有关。Sema4A 在血管生成和癌症中的功能尚未确定。最近的研究已经证明了 Sema4A 在血管内皮细胞中的表达和功能。然而，这些研究的结果存在争议，因为它们根据实验设置报告 Sema4A 具有促血管生成或抗血管生成作用。在这篇迷你综述中，我们讨论了这些发现以及我们关于 Sema4A 调节炎症和血管生成的研究结果，这两个都是肿瘤发生和肿瘤转移所强调的重要病理过程。了解 Sema4A 在这些过程中的作用可能有助于指导开发用于癌症的改进治疗方法。
