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水通道蛋白在癌症中的关键作用:聚焦血液系统恶性肿瘤

Critical Role of Aquaporins in Cancer: Focus on Hematological Malignancies.

作者信息

Allegra Alessandro, Cicero Nicola, Mirabile Giuseppe, Cancemi Gabriella, Tonacci Alessandro, Musolino Caterina, Gangemi Sebastiano

机构信息

Division of Hematology, Department of Human Pathology in Adulthood and Childhood "Gaetano Barresi", University of Messina, 98100 Messina, Italy.

Department of Biomedical, Dental, Morphological and Functional Imaging Sciences (BIOMORF), University of Messina, 98100 Messina, Italy.

出版信息

Cancers (Basel). 2022 Aug 29;14(17):4182. doi: 10.3390/cancers14174182.

Abstract

Aquaporins are transmembrane molecules regulating the transfer of water and other compounds such as ions, glycerol, urea, and hydrogen peroxide. Their alteration has been reported in several conditions such as cancer. Tumor progression might be enhanced by aquaporins in modifying tumor angiogenesis, cell volume adaptation, proteases activity, cell-matrix adhesions, actin cytoskeleton, epithelial-mesenchymal transitions, and acting on several signaling pathways facilitating cancer progression. Close connections have also been identified between the aquaporins and hematological malignancies. However, it is difficult to identify a unique action exerted by aquaporins in different hemopathies, and each aquaporin has specific effects that vary according to the class of aquaporin examined and to the different neoplastic cells. However, the expression of aquaporins is altered in cell cultures and in patients with acute and chronic myeloid leukemia, in lymphoproliferative diseases and in multiple myeloma, and the different expression of aquaporins seems to be able to influence the efficacy of treatment and could have a prognostic significance, as greater expression of aquaporins is correlated to improved overall survival in leukemia patients. Finally, we assessed the possibility that modifying the aquaporin expression using aquaporin-targeting regulators, specific monoclonal antibodies, and even aquaporin gene transfer could represent an effective therapy of hematological malignancies.

摘要

水通道蛋白是调节水以及离子、甘油、尿素和过氧化氢等其他化合物转运的跨膜分子。在癌症等多种情况下都有其改变的报道。水通道蛋白可通过改变肿瘤血管生成、细胞体积适应、蛋白酶活性、细胞与基质黏附、肌动蛋白细胞骨架、上皮-间质转化以及作用于促进癌症进展的多种信号通路来增强肿瘤进展。水通道蛋白与血液系统恶性肿瘤之间也已确定存在密切联系。然而,很难确定水通道蛋白在不同血液病中发挥的独特作用,而且每种水通道蛋白都有特定的效应,这会因所检测的水通道蛋白类别以及不同的肿瘤细胞而有所不同。不过,在细胞培养以及急性和慢性髓性白血病患者、淋巴增殖性疾病患者和多发性骨髓瘤患者中,水通道蛋白的表达都会发生改变,而且水通道蛋白的不同表达似乎能够影响治疗效果,并且可能具有预后意义,因为水通道蛋白的高表达与白血病患者总体生存率的提高相关。最后,我们评估了使用水通道蛋白靶向调节剂、特异性单克隆抗体甚至水通道蛋白基因转移来改变水通道蛋白表达是否可能成为血液系统恶性肿瘤的有效治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2451/9455074/6bc4e0196874/cancers-14-04182-g001.jpg

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