Basic Study
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World J Gastroenterol. Jan 14, 2015; 21(2): 453-464
Published online Jan 14, 2015. doi: 10.3748/wjg.v21.i2.453
Aberrant EphB/ephrin-B expression in experimental gastric lesions and tumor cells
Shintaro Uchiyama, Noritaka Saeki, Kazushige Ogawa
Shintaro Uchiyama, Noritaka Saeki, Kazushige Ogawa, Department of Veterinary Anatomy, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka 598-8531, Japan
Author contributions: Ogawa K designed the experiments and wrote the paper; Uchiyama S and Ogawa K performed the experiments; Ogawa K, Uchiyama S, and Saeki N analyzed the data.
Supported by Grant-in-Aid for Scientific Research from Japan Society for the Promotion of Science, No. 21580367 (to Ogawa K).
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Kazushige Ogawa, DVM, PhD, Department of Veterinary Anatomy, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku-Ourai-Kita, Izumisano, Osaka 598-8531, Japan. kogawa@vet.osakafu-u.ac.jp
Telephone: +81-72-4635584 Fax: +81-72-4635584
Received: March 27, 2014
Peer-review started: March 28, 2014
First decision: May 29, 2014
Revised: June 12, 2014
Accepted: July 22, 2014
Article in press: July 22, 2014
Published online: January 14, 2015
Processing time: 296 Days and 22.6 Hours
Abstract

AIM: To determine whether the expression profiles of EphB receptor and ephrin-B ligand can be used as markers for dysplastic/oncogenic transformation in gastric mucosa.

METHODS: The protein expression and localization of EphB and ephrin-B in normal, ulcerated regenerating, and dysplastic gastric mucosa were examined in a rat experimental model by immunolabeling, and mRNA expression was assessed in four human gastric carcinoma cell lines by reverse transcription-polymerase chain reaction.

RESULTS: Ephrin-B- and EphB-expressing regions were divided along the pit-gland axis in normal gastric units. EphB2 was transiently upregulated in the experimental ulcer, and its expression domain extended to gastric pits and/or the luminal surface where ephrin-B-expressing pit cells reside. EphB2, B3, and B4 and ephrin-B1 were coexpressed in the experimental gastric dysplasia, and more than one ligand-receptor pair was highly expressed in each of the gastric carcinoma cell lines.

CONCLUSION: Robust and stable coexpression of EphB and ephrin-B is a feature common to experimentally induced gastric dysplasia and human gastric carcinoma cell lines as compared to normal gastric and ulcerated regenerating epithelia. Thus, EphB/ephrin-B may be a useful marker combination for dysplastic/oncogenic transformation in gastric cancer.

Keywords: Gastric ulcer; Gastric dysplasia; Gastric carcinoma cell line; Coexpression; EphB; Ephrin-B

Core tip: A constant/high level of EphB and ephrin-B coexpression was identified as a feature common to experimentally induced gastric dysplasia and human gastric carcinoma cell lines, as compared to normal and regenerating gastric epithelia. Based on these, we proposed that the stable/robust EphB and ephrin-B coexpression is a marker of dysplastic/oncogenic transformation. Eph signaling in tumor cells likely has a suppressive role during tumor progression, with Eph and ephrin coexpressed on the same cell engaging in non-productive interactions via lateral inhibition and thereby silencing downstream signaling. These results can be useful for the early and accurate diagnosis of gastric tumors.