Brief Article
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World J Gastroenterol. Oct 28, 2011; 17(40): 4488-4495
Published online Oct 28, 2011. doi: 10.3748/wjg.v17.i40.4488
αV integrin: A new gastrin target in human pancreatic cancer cells
Celine Cayrol, Claudine Bertrand, Aline Kowalski-Chauvel, Laurence Daulhac, Elizabeth Cohen-Jonathan-Moyal, Audrey Ferrand, Catherine Seva
Celine Cayrol, Claudine Bertrand, Aline Kowalski-Chauvel, Elizabeth Cohen-Jonathan-Moyal, Audrey Ferrand, Catherine Seva, INSERM UMR1037-Cancer Research Center of Toulouse, Paul Sabatier University Toulouse III, 31432 Toulouse cedex 4, France
Laurence Daulhac, INSERM U766, Department of pharmacology, Clermont 1 University of Pharmacy, 63001 Clermont-Ferrand, France
Author contributions: Ferrand A and Seva C planned the study and wrote the paper; Daulhac L and Cohen-Jonathan-Moyal E contributed to the design of the study and critically revised the manuscript; Cayrol C, Bertrand C and Kowalski-Chauvel A were responsible for data acquisition and analysis.
Supported by Grants from INSERM
Correspondence to: Dr. Catherine Seva, INSERM UMR1037-Cancer Research Center of Toulouse, Paul Sabatier University Toulouse III, 1 avenue J Poulhes, BP 84225, 31432 Toulouse cedex 4, France. cathy.seva@inserm.fr
Telephone: +33-5-61322408 Fax: +33-5-61322403
Received: November 30, 2010
Revised: February 12, 2011
Accepted: February 19, 2011
Published online: October 28, 2011
Abstract

AIM: To analyse αV integrin expression induced by gastrin in pancreatic cancer models.

METHODS: αV integrin mRNA expression in human pancreatic cancer cells was analysed using a “cancer genes” array and confirmed by real-time reverse transcription-polymerase chain reaction (PCR). Western blotting and semi-quantitative immunohistochemistry were used to examine protein levels in human pancreatic cancer cell lines and pancreatic tissues, respectively. The role of αV integrin on gastrin-induced cell adhesion was examined using blocking anti-αV integrin monoclonal antibodies. Adherent cells were quantified by staining with crystal violet.

RESULTS: Using a “cancer genes” array we identified αV integrin as a new gastrin target gene in human pancreatic cancer cells. A quantitative real-time PCR approach was used to confirm αV integrin gene expression. We also demonstrate that Src family kinases and the PI 3-kinase, two signalling pathways specifically activated by the CCK-2 receptor (CCK2R), are involved in gastrin-mediated αV integrin expression. In contrast, inhibition of the ERK pathway was without any effect on αV integrin expression induced by gastrin. Our results also show that gastrin modulates cell adhesion viaαV integrins. Indeed, in vitro adhesion assays performed on fibronectin show that gastrin significantly increases adhesion of pancreatic cancer cells. The use of blocking anti-αV integrin monoclonal antibodies completely reversed the increase in cell-substrate adhesion induced by gastrin. In addition, we showed in vivo that the targeted CCK2R expression in the pancreas of Elas-CCK2 mice, leads to the overexpression of αV integrin. This process may contribute to pancreatic tumour development observed in these transgenic animals.

CONCLUSION: αV integrin is a new gastrin target in pancreatic cancer models and contributes to gastrin effects on cell adhesion.

Keywords: αV integrin; Cell adhesion; CCK-2 receptor; Gastrin; Pancreatic cancer