Maugeri Rosario, Schiera Gabriella, Di Liegro Carlo Maria, Fricano Anna, Iacopino Domenico Gerardo, Di Liegro Italia
Department of Experimental Biomedicine and Clinical Neurosciences (BIONEC), University of Palermo, Palermo I-90127, Italy.
Department of Biological Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo (UNIPA), Palermo I-90128, Italy.
Int J Mol Sci. 2016 Jun 29;17(7):1029. doi: 10.3390/ijms17071029.
Brain primary tumors are among the most diverse and complex human cancers, and they are normally classified on the basis of the cell-type and/or the grade of malignancy (the most malignant being glioblastoma multiforme (GBM), grade IV). Glioma cells are able to migrate throughout the brain and to stimulate angiogenesis, by inducing brain capillary endothelial cell proliferation. This in turn causes loss of tight junctions and fragility of the blood-brain barrier, which becomes leaky. As a consequence, the most serious clinical complication of glioblastoma is the vasogenic brain edema. Both glioma cell migration and edema have been correlated with modification of the expression/localization of different isoforms of aquaporins (AQPs), a family of water channels, some of which are also involved in the transport of other small molecules, such as glycerol and urea. In this review, we discuss relationships among expression/localization of AQPs and brain tumors/edema, also focusing on the possible role of these molecules as both diagnostic biomarkers of cancer progression, and therapeutic targets. Finally, we will discuss the possibility that AQPs, together with other cancer promoting factors, can be exchanged among brain cells via extracellular vesicles (EVs).
脑原发性肿瘤是人类最具多样性和复杂性的癌症之一,通常根据细胞类型和/或恶性程度进行分类(恶性程度最高的是多形性胶质母细胞瘤(GBM),IV级)。胶质瘤细胞能够在整个大脑中迁移,并通过诱导脑毛细血管内皮细胞增殖来刺激血管生成。这反过来会导致紧密连接的丧失和血脑屏障的脆弱性,使其变得渗漏。因此,胶质母细胞瘤最严重的临床并发症是血管源性脑水肿。胶质瘤细胞迁移和水肿都与水通道蛋白(AQP)不同异构体的表达/定位改变有关,水通道蛋白是一类水通道家族,其中一些还参与其他小分子如甘油和尿素的转运。在这篇综述中,我们讨论了水通道蛋白的表达/定位与脑肿瘤/水肿之间的关系,同时也关注这些分子作为癌症进展的诊断生物标志物和治疗靶点的可能作用。最后,我们将讨论水通道蛋白与其他癌症促进因子一起通过细胞外囊泡(EV)在脑细胞之间交换的可能性。