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天冬酰胺内肽酶的表达促进上皮性卵巢癌的生长潜能。

The expression of asparaginyl endopeptidase promotes growth potential in epithelial ovarian cancer.

作者信息

Zhu Qinyi, Tang Meiling, Wang Xipeng

机构信息

a Department of Gynecology , Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine , Shanghai , P.R. China.

出版信息

Cancer Biol Ther. 2017 Apr 3;18(4):222-228. doi: 10.1080/15384047.2017.1294290. Epub 2017 Mar 3.

Abstract

Epithelial ovarian cancer (EOC) is the most common and lethal cancer-related death among females in the world. Asparaginyl endopeptidase (AEP) is a member of C13 family peptidases and expressed in the extracellular matrix and tumor cells. The aim of this article is to explore the function of asparaginyl endopeptidase in epithelial ovarian cancer. The expression of AEP was examined in 20 EOC samples, 3 EOC metastasis samples, 6 fallopian tube metastasis samples, 4 peritoneum metastasis samples and 20 benign ovarian tumor samples by immunohistochemistry. The expression of AEP was also evaluated in serum and ascites of EOC patients by elisa. And we used a lentiviral vector to overexpress AEP in human epithelial ovarian cancer cell lines SKOV3ip and detected the function of AEP-SKOV3ip cells both in vitro and in vivo. The growth of AEP-SKOV3ip cells was observed by MTT, migration and tube formation assays in vitro. Additionally, the subcutaneous mice model was used to identify the tumor growth and metastasis in vivo. Mice tumors were stained for CD31 to determine the microvessel density (MVD). We demonstrated that AEP was highly expressed in the EOC patient tissues and ascites. The AEP transfected SKOV3ip cells could both promote tumor growth in vitro and in vivo. The MVD in AEP-SKOV3ip group was higher than that in NC-SKOV3ip group. Therefore, our results demonstrated that AEP could induce EOC growth and progressionboth in vitro and in vivo.

摘要

上皮性卵巢癌(EOC)是全球女性中最常见且致死率最高的癌症相关死因。天冬酰胺内肽酶(AEP)是C13家族肽酶的成员,在细胞外基质和肿瘤细胞中表达。本文旨在探讨天冬酰胺内肽酶在上皮性卵巢癌中的作用。通过免疫组织化学检测了20例EOC样本、3例EOC转移样本、6例输卵管转移样本、4例腹膜转移样本和20例良性卵巢肿瘤样本中AEP的表达。还通过酶联免疫吸附测定法评估了EOC患者血清和腹水中AEP的表达。我们使用慢病毒载体在人上皮性卵巢癌细胞系SKOV3ip中过表达AEP,并在体外和体内检测AEP-SKOV3ip细胞的功能。通过MTT法、体外迁移和管形成试验观察AEP-SKOV3ip细胞的生长。此外,使用皮下小鼠模型来鉴定体内肿瘤的生长和转移。对小鼠肿瘤进行CD31染色以确定微血管密度(MVD)。我们证明AEP在EOC患者组织和腹水中高表达。转染AEP的SKOV3ip细胞在体外和体内均可促进肿瘤生长。AEP-SKOV3ip组的MVD高于NC-SKOV3ip组。因此,我们的结果表明AEP在体外和体内均可诱导EOC生长和进展。

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