Published online Jan 14, 2015. doi: 10.3748/wjg.v21.i2.453
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
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.
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.