吴安玥;李栋;邱兴堤;邱丽华;

• 1:上海交通大学医学院附属仁济医院妇产科上海市妇科肿瘤重点实验室

摘要(Abstract)：

目的:探讨成纤维细胞生长诱导因子14(Fn14)在上皮性卵巢癌转移中的作用。方法:选取人上皮性卵巢癌细胞株HO8910及其配对高转移能力细胞株HO8910-PM。Western blot法检测HO8910、HO8910-PM细胞株中Fn14表达,以及Fn14过表达质粒转染HO8910-PM细胞株后Fn14、Slug、MMP-9蛋白的表达情况。Transwell实验检测细胞株体外迁移和侵袭能力。结果:HO8910-PM细胞的迁移和侵袭细胞数均多于HO8910细胞(P<0.05)。HO8910-PM细胞中Fn14表达水平明显低于HO8910细胞(P<0.05)。Fn14过表达质粒转染HO8910-PM细胞后,细胞内Fn14表达水平上调(5.4±0.314)倍(P<0.05),细胞的迁移和侵袭能力明显降低,同时细胞中侵袭转移相关蛋白Slug和MMP-9表达明显下降(P<0.05)。结论:Fn14可能通过下调Slug和MMP-9表达进而抑制上皮性卵巢癌细胞的侵袭转移,Fn14可能为临床治疗上皮性卵巢癌提供新靶标。

关键词(KeyWords)： 卵巢肿瘤;Fn14;转移;Slug;MMP-9

Abstract:

Keywords:

基金项目(Foundation): 上海市教科委重点学科,国家自然基金资助项目(No:81272884)

作者(Authors): 吴安玥;李栋;邱兴堤;邱丽华;

DOI: 10.13283/j.cnki.xdfckjz.2016.03.002

参考文献(References)：

• [1]Torre LA,Bray F,Siegel RL,et al.Global cancer statistics[J].CA Cancer J Clin,2015,65(2):87-108
• [2]Sunila P,Kim SW,Wu SY,et al.Abstract 4954:Hematogenous metastasis of ovarian cancer:Re-thinking mode of spread[J].Cancer Research,2014,74(1):4954-4954
• [3]Meighan-Mantha RL,Hsu DK,Guo Y,et al.The mitogeninducible Fn14 gene encodes a type I transmembrane protein that modulates fibroblast adhesion and migration[J].J Biol Chem,1999,274(46):33166-33176
• [4]Winkles JA.The TWEAK-Fn14 cytokine-receptor axis:discovery,biology and therapeutic targeting[J].Nat Rev Drug Discov,2008,7(5):411-25
• [5]Cheng E,Whitsett TG,Tran NL,et al.The TWEAK receptor Fn14 is an Src-inducible protein and a positive regulator of Src-driven cell invasion[J].Mol Cancer Res,2015,13(3):575-583
• [6]Alexandra A,Shira A,Prigozhina TB,et al.Fn14·TRAIL effectively inhibits hepatocellular carcinoma growth[J].Plos One,2013,8(10):1002-1004
• [7]Gu L,Dai L,Cao C,et al.Functional expression of TWEAK and the receptor Fn14 in human malignant ovarian tumors:possible implication for ovarian tumor intervention[J].Plos One,2013,8(3):e57436
• [8]Asrani K,Keri RA,Galisteo R,et al.The HER2-and heregulinβ1(HRG)-inducible TNFR superfamily member Fn14promotes HRG-driven breast cancer cell migration,invasion,and MMP9 expression[J].Mol Cancer Res Mcr,2013,11(4):393
• [9]Watts GS,Tran NL,Berens ME,et al.Identification of Fn14/TWEAK receptor as a potential therapeutic target in esophageal adenocarcinoma.[J].Int J Cancer,2007,121(10):2132-2139
• [10]Whitsett TG,Ensign SPF,Dhruv HD,et al.FN14 expression correlates with MET in NSCLC and promotes METdriven cell invasion[J].Clin Exp Metastas,2014,31(6):613-623
• [11]Wang D,Fung JNT,Tuo Y,et al.TWEAK/Fn14 promotes apoptosis of human endometrial cancer cells via caspase pathway[J].Cancer Lett,2010,294(1):91-100
• [12]Jing Y,Di C,Guo W,et al.Activated androgen receptor promotes bladder cancer metastasis via Slug mediated epithelial-mesenchymal transition[J].Cancer Lett,2014,348(1-2):135-145
• [13]Hongyan J,Yinhua Y,Tao Z,et al.Snail is critical for tumor growth and metastasis of ovarian carcinoma[J].Int J Cancer,2010,126(9):2102-2111
• [14]Phillips S,Prat A,Sedic M,et al.Cell-State Transitions Regulated by SLUG Are Critical for Tissue Regeneration and Tumor Initiation[J].Stem Cell Reports,2014,2(5):633-647
• [15]Kurrey NK,Amit K,Bapat SA.Snail and Slug are major determinants of ovarian cancer invasiveness at the transcription level[J].Gynecol Oncol,2005,97(1):155-165
• [16]Fraga CADC,Farias LC,Pereira CS,et al.Increased VEGFR2 and MMP9 protein levels are associated with epithelial dysplasia grading[J].Pathol Res Prac,2014,210(12):959-964
• [17]Jacob A,Jing J,Lee J,et al.Rab40b regulates trafficking of MMP2 and MMP9 during invadopodia formation and invasion of breast cancer cells[J].J Cell Sci,2013,126(Pt20):4647-4658
• [18]Ashok-Kumar D,Prasanna E,Yande G,et al.Platelet-type12-lipoxygenase induces MMP9 expression and cellular invasion via activation of PI3K/Akt/NF-κB[J].Int J Cancer,2013,133(8):1784-1791
• [19]Winiarski BK,Cope N,Alexander M,et al.Clinical relevance of increased endothelial and mesothelial expression of proangiogenic proteases and VEGFA in the omentum of patients with metastatic ovarian high-grade serous carcinoma 1 2[J].Translational Oncol,2014,7(2):267-276
• [20]Naora H,Montell DJ.Ovarian cancer metastasis:integrating insights from disparate model organisms[J].Nat Rev Cancer,2005,5(5):355-366