Yakabe Kazuyuki, Murakami Akihiro, Kajimura Takuya, Nishimoto Yuki, Sueoka Kotaro, Sato Shun, Nawata Shugo, Sugino Norihiro
Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
J Obstet Gynaecol Res. 2016 May;42(5):566-72. doi: 10.1111/jog.12935. Epub 2016 Feb 18.
Transgelin-2 (TAGLN2) has previously been found to be highly expressed in uterine cervical squamous cell carcinoma (SCC) tissues by proteomic analyses. The present study investigated the role of TAGLN2 in the malignant behaviors of cervical SCC cells in vitro and in vivo, and the clinical significance of TAGLN2 using immunohistochemistry for human cervical SCC tissues.
Antisense (AS) constructs of TAGLN2 cDNA (AS clones) and the empty vector (control clone) were transfected into a human uterine SCC cell line (SKG IIIa), and malignant behaviors were analyzed in vitro. In an in vivo experiment, 10(7) cells of the AS and control clones were subcutaneously inoculated into female BALB/c nude mice. In immunohistochemistry with anti-TAGLN2 antibodies for human cervical SCC, FIGO stage IA and IB (n = 75), the expression patterns of TAGLN2 were divided into two groups: weak and strong. The relation between expression pattern and prognosis was analyzed.
Suppression of TAGLN2 inhibited cancer cell migration and secretion of matrix metalloproteinases. Tumors in the control clone group continued to grow, whereas those in the AS clone group clearly stopped growing. Six weeks after injection, the tumor size was significantly smaller in the AS clone group than in the control clone group. Immunohistochemistry revealed that the strong pattern was associated with poor overall survival compared with the weak pattern by the Kaplan-Meier method.
TAGLN2 plays functional roles in the progression of cervical SCC. Suppression of TAGLN2 may be a new strategy for the treatment of cervical SCC.
先前通过蛋白质组学分析发现,转胶蛋白-2(TAGLN2)在子宫颈鳞状细胞癌(SCC)组织中高表达。本研究调查了TAGLN2在体外和体内宫颈SCC细胞恶性行为中的作用,以及使用免疫组织化学方法检测TAGLN2在人宫颈SCC组织中的临床意义。
将TAGLN2 cDNA的反义(AS)构建体(AS克隆)和空载体(对照克隆)转染到人子宫SCC细胞系(SKG IIIa)中,并在体外分析其恶性行为。在体内实验中,将10^7个AS克隆和对照克隆的细胞皮下接种到雌性BALB/c裸鼠体内。在对人宫颈SCC进行抗TAGLN2抗体免疫组织化学检测时,国际妇产科联盟(FIGO)分期为IA和IB期(n = 75),TAGLN2的表达模式分为两组:弱表达和强表达。分析表达模式与预后的关系。
抑制TAGLN2可抑制癌细胞迁移和基质金属蛋白酶的分泌。对照克隆组的肿瘤继续生长,而AS克隆组的肿瘤明显停止生长。注射后六周,AS克隆组的肿瘤大小明显小于对照克隆组。免疫组织化学显示,通过Kaplan-Meier方法分析,与弱表达模式相比,强表达模式与总体生存率较差相关。
TAGLN2在宫颈SCC进展中发挥功能性作用。抑制TAGLN2可能是治疗宫颈SCC的一种新策略。