Skip Navigation



Carcinogenesis Advance Access published online on June 26, 2008
Carcinogenesis, doi:10.1093/carcin/bgn134
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
29/10/1994    most recent
bgn134v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Mima, S.
Right arrow Articles by Mizushima, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mima, S.
Right arrow Articles by Mizushima, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

NSAIDs Suppress the Expression of Claudin-2 to Promote Invasion Activity of Cancer Cells

Shinji Mima, Masaya Takehara, Hiroko Takada, Tomoko Nishimura, Tatsuya Hoshino and Tohru Mizushima*

Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan

* Correspondence: T Mizushima, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan. Phone & FAX: 81-96-371-4323; E-mail: mizu{at}gpo.kumamoto-u.ac.jp

Non-steroidal anti-inflammatory drugs (NSAIDs) show chemopreventive effects, however, the precise molecular mechanism of these effects is still unclear. On the other hand, the expression of proteins that form tight junctions (such as claudins) in clinically isolated tumors is frequently altered relative to normal tissue. We previously reported that NSAIDs up-regulate the expression of claudin-4 and that this up-regulation contributes to NSAID-dependent inhibition of both migration activity and anchorage-independent growth of cancer cells. In the current study, we have systematically examined the effects of various NSAIDs on the expression of various tight junction proteins and have found that NSAIDs specifically and drastically inhibit the expression of claudin-2. Overexpression or suppression of claudin-2 expression caused stimulation or inhibition, respectively, of the invasion and migration activity of cancer cells. Furthermore, NSAIDs inhibited the invasion and migration activity of cancer cells and this inhibition was suppressed by overexpression of claudin-2. In contrast, neither cell growth nor apoptosis induced by lack of anchorage of cancer cells were affected by overexpression or suppression of expression of claudin-2. These results suggest that inhibition of claudin-2 expression by NSAIDs contributes to NSAID-dependent inhibition of invasion of cancer cells in vitro and that it may be involved in the chemopreventive effects of NSAIDs by inhibiting metastasis in vivo.

Key Words: NSAIDs • tight junction • claudin-2 • invasion • cancer

Received February 1, 2008; revised April 28, 2008; accepted May 27, 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Mol. Cell. Biol.Home page
A.-L. Cattin, J. Le Beyec, F. Barreau, S. Saint-Just, A. Houllier, F. J. Gonzalez, S. Robine, M. Pincon-Raymond, P. Cardot, M. Lacasa, et al.
Hepatocyte Nuclear Factor 4{alpha}, a Key Factor for Homeostasis, Cell Architecture, and Barrier Function of the Adult Intestinal Epithelium
Mol. Cell. Biol., December 1, 2009; 29(23): 6294 - 6308.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.