Clinical and biological significance of tissue transglutaminase in ovarian carcinoma.
Clinical and biological significance of tissue transglutaminase in ovarian carcinoma.
复制标题
DOI：
10.1158/0008-5472.can-07-6130
复制
发表时间：
2008-07-15
期刊：
影响因子：
11.2
通讯作者：
Sood AK
中科院分区：
文献类型：
--
作者：
Hwang JY;Mangala LS;Fok JY;Lin YG;Merritt WM;Spannuth WA;Nick AM;Fiterman DJ;Vivas-Mejia PE;Deavers MT;Coleman RL;Lopez-Berestein G;Mehta K;Sood AK
组织型转氨酶（TG 2）是一种独特的多功能蛋白质，在癌症转移级联的许多步骤中发挥作用。在这里，我们研究了临床（n = 93上皮性卵巢癌）和生物学（体外粘附，侵袭，生存和体内治疗靶向）的意义TG 2在卵巢癌。在单变量和多变量分析中，TG 2的过度表达与患者总体生存率显著降低相关。TG 2转染SKOV 3 ip 1细胞促进纤维连接蛋白包被的表面上的附着和扩散，并增加这些细胞的体外侵袭潜力。相反，用HeyA 8细胞的siRNA沉默TG 2显著降低了细胞的侵袭潜力，并且还增加了紫杉醇诱导的细胞死亡。使用化疗敏感（HeyA 8）和耐药（HeyA 8-MDR，RMG 2）模型的体内治疗实验证明了单独使用TG 2 siRNA-DOPC和与多西他赛化疗组合的显著抗肿瘤活性。这种抗肿瘤活性与体内增殖、血管生成减少和肿瘤细胞凋亡增加有关。总之，这些发现表明，TG 2过表达是卵巢癌的不良预后因素，TG 2靶向治疗可能是一种有吸引力的治疗方法。
Tissue type transglutaminase (TG2) is a unique multifunctional protein that plays a role in many steps in the cancer metastatic cascade. Here, we examined the clinical (n = 93 epithelial ovarian cancers) and biological (in vitro adhesion, invasion, and survival and in vivo therapeutic targeting) significance of TG2 in ovarian cancer. The overexpression of TG2 was associated with significantly worse overall patient survival in both univariate and multivariate analyses. Transfection of TG2 into the SKOV3ip1 cells promoted attachment and spreading on fibronectin-coated surfaces and increased the in vitro invasive potential of these cells. Conversely, TG2 silencing with siRNA of HeyA8 cells significantly decreased the invasive potential of the cells, and also increased docetaxel-induced cell death. In vivo therapy experiments using chemotherapy-sensitive (HeyA8) and resistant (HeyA8-MDR, RMG2) models demonstrated significant anti-tumor activity both with TG2 siRNA-DOPC alone and in combination with docetaxel chemotherapy. This anti-tumor activity was related to decreased proliferation, angiogenesis and increased tumor cell apoptosis in vivo. Taken together, these findings indicate that TG2 overexpression is an adverse prognostic factor in ovarian carcinoma and TG2 targeting may be an attractive therapeutic approach.