KAI1调控Integrinβ1通路抑制卵巢癌侵袭、转移
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摘要
目的探讨KAI1通过调控Integrinβ1通路抑制卵巢癌侵袭的可能机制。方法采用免疫组化En Vision法检测60例上皮性卵巢癌组织、25例正常卵巢组织、21例良性上皮性卵巢肿瘤组织中KAI1蛋白与Integrinβ1蛋白表达的关系; Western blot法检测KAI1在人上皮性卵巢癌细胞株A2780、HO-8910、SKOV3细胞和人正常卵巢上皮细胞株HOSEpi C中的表达;构建高表达质粒EGFP-KAI1转染HO-8910细胞株后,使用Western blot法检测KAI1、Integrinβ1、MMP-7、MMP-9的表达。结果随着上皮性卵巢癌病理学分级及临床分期的增高,KAI1蛋白阳性率降低,Integrinβ1蛋白阳性率升高,KAI1与Integrinβ1表达呈负相关(P <0. 05),在卵巢癌细胞株上亦观察到相似结果;相对于对照组,KAI1高表达组中Integrinβ1、MMP-7、MMP-9表达下调,细胞侵袭、转移能力下降。结论 KAI1可能通过调控Integrinβ1通路抑制卵巢癌侵袭、转移,为探究KAI1抑制肿瘤发生、发展提供新思路。
引文
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[6]Siegel R L,Miller K D,Jemal A.Cancer statistics,2017[J].CACancer J Clin,2017,67(1):7-30.
[7]Schindl M,Birner P,Breitenecker G,et al.Downregulation of KAI1 metastasis suppressor protein is associated with a dismal prognosis in epithelial ovarian cancer[J].Gynecol Oncol,2001,83(2):244-248.
[8]Paolillo M,Schinelli S.Integrins and exosomes,a dangerous liaison in cancer progression[J].Cancers(Basel),2017,9(8):1-8.
[9]MulleR-Klingspor V,Hefler L,Obermair A,et al.Prognostic value of beta1-integrin(CD29)in serous adenocarcinomas of the ovary[J].Anticancer Res,2001,21(3C):2185-2188.
[10]刘静,张柳,杨勇,等.卵巢癌组织CXCL12、MMP-9、integrinβ1表达及意义[J].山东医药,2016,28:50-52.
[11]Chen J,Khalil R A.Matrix metallo proteinases in normal pregnancy and preeclampsia[J].Prog Mol Biol Transl Sci,2017,148:87-165.
[12]Alaseem A,Alhazzani K,Dondapati P,et al.Matrix metallo proteinases:a challenging paradigm of cancer management[J].Semin Cancer Biol,2017,11:1-17.
[2]Houle C D,Ding X Y,Foley J F,et al.Loss of expression and altered localization of KAI1 and CD9 protein are associated with epithelial ovarian cancer progression[J].Gynecol Oncol,2002,86(1):69-78.
[3]张丽娟,王秋红,汤春生.转移抑制基因KAI1与卵巢癌临床病理因素和预后的关系[J].中国妇幼保健,2008,23(24):3443-3446.
[4]张健,吕飒美,赵素平,等.人Kai-1基因真核表达载体的构建及其体外表达[J].科学技术与工程,2014,14(33):16-19.
[5]马大烈,白辰光.免疫组织化学阳性标记结果的观察和判断[J].临床与实验病理学杂志,2003,19(5):557-559.
[6]Siegel R L,Miller K D,Jemal A.Cancer statistics,2017[J].CACancer J Clin,2017,67(1):7-30.
[7]Schindl M,Birner P,Breitenecker G,et al.Downregulation of KAI1 metastasis suppressor protein is associated with a dismal prognosis in epithelial ovarian cancer[J].Gynecol Oncol,2001,83(2):244-248.
[8]Paolillo M,Schinelli S.Integrins and exosomes,a dangerous liaison in cancer progression[J].Cancers(Basel),2017,9(8):1-8.
[9]MulleR-Klingspor V,Hefler L,Obermair A,et al.Prognostic value of beta1-integrin(CD29)in serous adenocarcinomas of the ovary[J].Anticancer Res,2001,21(3C):2185-2188.
[10]刘静,张柳,杨勇,等.卵巢癌组织CXCL12、MMP-9、integrinβ1表达及意义[J].山东医药,2016,28:50-52.
[11]Chen J,Khalil R A.Matrix metallo proteinases in normal pregnancy and preeclampsia[J].Prog Mol Biol Transl Sci,2017,148:87-165.
[12]Alaseem A,Alhazzani K,Dondapati P,et al.Matrix metallo proteinases:a challenging paradigm of cancer management[J].Semin Cancer Biol,2017,11:1-17.