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BioMed Research International
Volume 2013, Article ID 917296, 8 pages
http://dx.doi.org/10.1155/2013/917296
Research Article

The Cell Surface GRP78 Facilitates the Invasion of Hepatocellular Carcinoma Cells

1Central Laboratory, Liaoning Medical College, Jinzhou, Liaoning 121001, China
2Oncology Department, The First Affiliated Hospital of Liaoning Medical College, Jinzhou, Liaoning 121001, China
3College of Pharmacy, Liaoning Medical College, Jinzhou, Liaoning 121001, China
4Traditional Chinese Department, The First Affiliated Hospital of Liaoning Medical College, Jinzhou, Liaoning 121001, China
5Developmental Biology Department, Liaoning Medical College, Jinzhou, Liaoning 121001, China
6Medical Genetics Department, Liaoning Medical College, Jinzhou, Liaoning 121001, China

Received 6 October 2013; Accepted 18 November 2013

Academic Editor: Paul Higgins

Copyright © 2013 Xiu-Xiu Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Invasion is a major characteristic of hepatocellular carcinoma and one of the main causes of refractory to treatment. We have previously reported that GRP78 promotes the invasion of hepatocellular carcinoma although the mechanism underlying this change remains uncertain. In this paper, we explored the role of the cell surface GRP78 in the regulation of cancer cell invasion in hepatocellular carcinoma cells. We found that neutralization of the endogenous cell surface GRP78 with the anti-GRP78 antibody inhibited the adhesion and invasion in hepatocellular carcinoma cell lines Mahlavu and SMMC7721. However, forced expression of the cell surface GRP78 facilitated the adhesion and invasion in SMMC7721. We further demonstrated that inhibition of the endogenous cell surface GRP78 specifically inhibited the secretion and activity of MMP-2 but did not affect the secretion and activity of MMP-9. We also found that inhibition of the cell surface GRP78 increased E-Cadherin expression and decreased N-Cadherin level. On the contrary, forced expression of the cell surface GRP78 increased N-Cadherin expression and decreased E-Cadherin level, suggesting that the cell surface GRP78 plays critical role in the regulation of EMT process. These findings suggest that the cell surface GRP78 plays a stimulatory role in the invasion process and may be a potential anti-invasion target for the treatment of hepatocellular carcinoma.