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

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

Author information

1
Department of Pathology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
2
Department of Obstetrics and Gynecology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
3
Division of Cancer Cell Research, Kanagawa Cancer Center Research Institute, Kanagawa, Japan.
4
Department of Pathology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan kaznabes@fukuoka-u.ac.jp.

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.

KEYWORDS:

EphA2; MT1-MMP; ovarian tumours; processing

PMID:
29970559
DOI:
10.21873/anticanres.12722
[Indexed for MEDLINE]

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