Department of Pathology, Kanazawa Medical University, Daigaku 1-1, Uchinada-machi, Kahoku-gun, 920-0293 Ishikawa, Japan.
Department of Orthopedic Surgery, Graduate School of Medical Science, Kanazawa University, 13-1, Takara-machi, Kanazawa, 920-8641 Ishikawa, Japan.
Pathol Res Pract. 2018 Jan;214(1):80-88. doi: 10.1016/j.prp.2017.11.006. Epub 2017 Nov 12.
Recent studies of several carcinomas have reported that aquaporin possesses novel oncogenic properties. The aim of this study was to clarify the involvement of aquaporin-1 and -5 in the proliferation, invasion and metastasis of soft tissue sarcomas.
The expression of aquaporin-1 and -5 was immunohistochemically examined in 73 soft tissue sarcomas as well as in benign, locally aggressive soft tissue tumors, and in soft tissues of adult humans and human fetuses. The mRNA and protein expression of aquaporin-1 and -5 genes were quantified in 19 sarcoma tissues.
Aquaporin-1 was expressed in the tumor cells of 37 (51%) and aquaporin-5 in 29 (40%) of 73 soft tissue sarcomas. Two expression patterns were identified: a differentiation-dependent pattern, similar to their expression in adult human soft tissue and in benign soft tissue tumors, and an aggressiveness-related pattern, that is similar to their expression in the mesenchymal cells of the developing fetal limb. The latter expression pattern proved to be an independent prognostic factor for patients with soft tissue sarcoma, in which aquaporin-1 was related to the invasiveness, and aquaporin-5 to the proliferation of soft tissue sarcoma cells.
These results indicate pivotal roles for aquaporin-1 and -5 in the aggressive growth and metastatic potential of soft tissue sarcomas, suggesting that they are promising targets for the treatment of patients with intractable soft tissue sarcoma.
最近的几项癌症研究报告称,水通道蛋白具有新的致癌特性。本研究旨在阐明水通道蛋白-1 和 -5 在软组织肉瘤的增殖、侵袭和转移中的作用。
采用免疫组织化学方法检测 73 例软组织肉瘤、良性局部侵袭性软组织肿瘤以及成人和胎儿软组织中 aquaporin-1 和 -5 的表达。定量检测 19 例肉瘤组织中 aquaporin-1 和 -5 基因的 mRNA 和蛋白表达。
73 例软组织肉瘤中,37 例(51%)表达 aquaporin-1,29 例(40%)表达 aquaporin-5。鉴定出两种表达模式:一种是与成人软组织和良性软组织肿瘤相似的分化依赖性模式,另一种是与发育中胎儿肢体间充质细胞相似的侵袭性相关模式。后者被证明是软组织肉瘤患者的独立预后因素,其中 aquaporin-1 与软组织肉瘤细胞的侵袭性有关,而 aquaporin-5 与增殖有关。
这些结果表明 aquaporin-1 和 -5 在软组织肉瘤的侵袭性生长和转移潜能中发挥关键作用,表明它们是治疗难治性软组织肉瘤患者的有前途的靶点。