Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Cancer Lett. 2018 Feb 1;414:81-87. doi: 10.1016/j.canlet.2017.11.010. Epub 2017 Nov 10.
Gliomas are highly invasive brain tumors with increased resistance to chemotherapy and high recurrence rate. Neoplastic cells commonly infiltrate into the surrounding tissue even at low grade tumors. Cell migration is often ceased at white and grey matter junctions indicating the involvement of tropic and axon guidance molecules in glioma growth and invasion. Emerging evidence implicates plexin-semaphorin signaling in the pathobiology of gliomas. Plexins are transmembrane receptors divided into four subfamilies (Plexins-A to -D) with differential specificity and functionality. They are involved in cell adhesion and motility, vascular growth and organogenesis, as well as tumor progression. In gliomas, plexins-A serve as coreceptors of neuropilins and transduce signals of class 3 semaphorins to PI3K/Akt pathway promoting cell growth, migration and invasion. Plexins-B1 and -B2 bind class 4 semaphorins to regulate RhoGTPases and induce glioma invasiveness and angiogenesis while, plexins-B3 interact with class 5 semaphorins to inhibit cell invasion and promote astrocytic cell differentiation via glial fibrillary acidic protein (GFAP) regulation. This review focuses on the biological roles of plexin-semaphorin signaling in glioma pathogenesis and discusses their potential as prognostic biomarkers and therapeutic targets.
神经胶质瘤是一种高度侵袭性的脑肿瘤，对化疗有较强的耐药性，且复发率较高。即使在低度肿瘤中，肿瘤细胞也常常浸润到周围组织。细胞迁移通常在白质和灰质交界处停止，这表明趋化因子和轴突导向分子参与了神经胶质瘤的生长和侵袭。新出现的证据表明，丛蛋白-神经递质信号在神经胶质瘤的病理生物学中起作用。丛蛋白是一种跨膜受体，分为四个亚家族（丛蛋白-A 到 -D），具有不同的特异性和功能。它们参与细胞黏附和运动、血管生成和器官发生，以及肿瘤进展。在神经胶质瘤中，丛蛋白-A 作为神经纤毛蛋白的核心受体，转导 3 类神经递质的信号，促进细胞生长、迁移和侵袭。丛蛋白-B1 和 -B2 结合 4 类神经递质，调节 RhoGTPases，诱导神经胶质瘤的侵袭和血管生成，而丛蛋白-B3 与 5 类神经递质相互作用，通过胶质纤维酸性蛋白（GFAP）调节抑制细胞侵袭，促进星形胶质细胞分化。本文综述了丛蛋白-神经递质信号在神经胶质瘤发病机制中的生物学作用，并讨论了它们作为预后生物标志物和治疗靶点的潜力。
