Du Peng, Wang Shuo, Tang Xingxing, An Chao, Yang Yong, Jiang Wen G
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Urology, Peking University Cancer Hospital & Institute, Beijing, P.R. China.
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Urology, Peking University Cancer Hospital & Institute, Beijing, P.R. China
Anticancer Res. 2017 Aug;37(8):4499-4505. doi: 10.21873/anticanres.11846.
Metastasis suppressor 1 (MTSS1) is a multi-functional cytoskeletal protein. Recent research showed that MTSS1 is a potential tumor suppressor in many types of cancer cells, including kidney and bladder cancer cells. However, the clinical implication of MTSS1 in human bladder uroepithelium cell carcinoma (BUCC) and its potential in suppressing BUCC tumorigenesis remains undetermined. In the present study, the expression of MTSS1 in human BUCC tissue samples, and correlations between MTSS1 and pathological grade and stage of the tumors were examined in BUCC specimens. The function of MTSS1 in BUCC progression was explored.
The mRNA and protein expression of MTSS1 were examined in 68 BUCC tissue samples with matching adjacent normal bladder tissues using quantitative real-time PCR and western blotting. Furthermore, the bladder cancer cell line 5637 was used to determine the anticancer effect of MTSS1.
Lower MTSS1 mRNA expression was recorded in BUCC tissues compared to normal bladder tissues. A lower MTSS1 mRNA level was observed in tumors with high clinical stage and with high pathological nuclear grade. Likewise, MTSS1 protein expression in normal bladder tissue was significantly higher than that in BUCC tissue. The protein level of MTSS1 significantly negatively correlated with clinical stage and pathological nuclear grade of BUCC. Cumulative survival curves indicated that MTSS1 expression was negatively correlated with survival time: patients with a high level of MTSS1 had significantly longer survival time than those with a low level of MTSS1 (p<0.001). Overexpression of MTSS1 reduced BUCC cell proliferation, cell-cycle progression and colony formation, but had no influence on BUCC cell apoptosis.
Overexpression of MTSS1 suppresses BUCC development, providing a novel perspective for BUCC tumorigenesis and a potential therapeutic target for BUCC.
转移抑制因子1（MTSS1）是一种多功能细胞骨架蛋白。近期研究表明，MTSS1在包括肾癌细胞和膀胱癌细胞在内的多种癌细胞中是一种潜在的肿瘤抑制因子。然而，MTSS1在人膀胱尿路上皮细胞癌（BUCC）中的临床意义及其抑制BUCC肿瘤发生的潜力仍未明确。在本研究中，检测了MTSS1在人BUCC组织样本中的表达，以及MTSS1与肿瘤病理分级和分期之间的相关性，并在BUCC标本中进行了研究。探讨了MTSS1在BUCC进展中的作用。
使用定量实时PCR和蛋白质印迹法检测了68例BUCC组织样本及其匹配的相邻正常膀胱组织中MTSS1的mRNA和蛋白表达。此外，使用膀胱癌细胞系5637来确定MTSS1的抗癌作用。
与正常膀胱组织相比，BUCC组织中MTSS1 mRNA表达较低。在临床分期高和病理核分级高的肿瘤中观察到较低的MTSS1 mRNA水平。同样，正常膀胱组织中MTSS1蛋白表达明显高于BUCC组织。MTSS1蛋白水平与BUCC的临床分期和病理核分级呈显著负相关。累积生存曲线表明，MTSS1表达与生存时间呈负相关：MTSS1水平高的患者生存时间明显长于MTSS1水平低的患者（p<0.001）。MTSS1的过表达降低了BUCC细胞的增殖、细胞周期进程和集落形成，但对BUCC细胞凋亡没有影响。
MTSS1的过表达抑制了BUCC的发展，为BUCC的肿瘤发生提供了新的视角，并为BUCC提供了潜在的治疗靶点。
