MT1-MMP介导的EphA2激活过程参与卵巢肿瘤的恶性转化。

Activated EphA2 Processing by MT1-MMP Is Involved in Malignant Transformation of Ovarian Tumours .

作者信息

Takahashi Yoko, Hamasaki Makoto, Aoki Mikiko, Koga Kaori, Koshikawa Naohiko, Miyamoto Shingo, Nabeshima Kazuki

机构信息

Department of Pathology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

Department of Obstetrics and Gynecology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

出版信息

Anticancer Res. 2018 Jul;38(7):4257-4266. doi: 10.21873/anticanres.12722.

DOI:10.21873/anticanres.12722

PMID:29970559

Abstract

BACKGROUND/AIM: Erythropoietin-producing hepatocellular receptor-2 (EphA2) is overexpressed in ovarian cancer. The N-terminals of EphA2 are processed by membrane-type 1 matrix metalloproteinase (MT1-MMP) and can subsequently induce ligand-independent signal activation to promote motility, invasion, and metastasis. The aim of this study was to investigate whether EphA2 processing occurs in benign, borderline, and malignant ovarian tumours.

MATERIALS AND METHODS

Overall 107 ovarian epithelial carcinomas (OECs; 47 serous, 24 endometrioid, 16 mucinous, and 20 clear cell), 54 ovarian borderline tumours (OBTs; 12 serous, 42 mucinous), and 45 adenomas (15 serous, 17 mucinous, and 13 endometriotic cysts) were evaluated. Expression and processing of EphA2 were semi-quantitatively analyzed. EphA2 processing was also investigated by immunoblotting.

RESULTS

EphA2 and MT1-MMP co-expression were detected. N-terminal EphA2 levels were significantly lower than those of C-terminal EphA2 in OECs and OBTs, but not in adenomas. Immunoblotting revealed processed fragments in OEC and OBTs.

CONCLUSION

EphA2 processing by MT1-MMP is associated with malignant transformation in ovarian tumours.

摘要

背景/目的：促红细胞生成素产生肝细胞受体2（EphA2）在卵巢癌中过度表达。EphA2的N端由膜型1基质金属蛋白酶（MT1-MMP）加工处理，随后可诱导非配体依赖性信号激活，从而促进细胞运动、侵袭和转移。本研究旨在探讨EphA2的加工处理是否发生在良性、交界性和恶性卵巢肿瘤中。

材料与方法

共评估了107例卵巢上皮癌（OEC；47例浆液性、24例子宫内膜样、16例黏液性和20例透明细胞癌）、54例卵巢交界性肿瘤（OBT；12例浆液性、42例黏液性）和45例腺瘤（15例浆液性、17例黏液性和13例子宫内膜异位囊肿）。对EphA2的表达和加工处理进行了半定量分析。还通过免疫印迹法研究了EphA2的加工处理情况。