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NEPHRONECTIN REGULATES INTESTINAL EPITHELIUM-MESENCHYME INTERCOMMUNICATION THROUGH INTEGRIN alpha8beta1
YD Benoit, I Teller, JF Groulx, E Herring, J-F Beaulieu*
Équipe IRSC sur l’épithélium digestif, Département d’anatomie et biologie cellulaire, Faculté de médecine et des sciences de la santé, Université de Sherbrooke
INTRODUCTION: Integrin alpha8beta1 interacts in an RGD dependent way with the extracellular matrix in order to control various physiological mechanisms such as cell adhesion, migration and proliferation as well as cell survival. The interaction between nephronectin (NPNT), an element of the extracellular matrix expressed by epithelial cells, and alpha8beta1 has been well documented in the foetal kidney. Recently, it has been shown that the alpha8beta1-NPNT interaction was involved in gene expression regulation in the mesenchyme. Moreover, in mice, breast primary tumours having strong metastatic potential over-express NPNT compared to those with low metastatic potential. These data suggest a role for the alpha8beta1-NPNT interaction in epithelium-stromal cross-talk regulation.
OBJECTIVE: The object of our work was to characterize alpha8beta1-NPNT in human intestine and to study the role of this interaction in the progression of biological processes such as development and cancer.
RESULTS: By western blot and RT-PCR, we have shown that NPNT, normally expressed at low amounts in colonocytes, is strongly produced and deposited at the basement membrane of the colon cancer cell line, Caco-2/15. Co-culture experiments have confirmed that NPNT was targeted at the epithelium-mesenchyme interface. These co-culture experiments also suggest a role for alpha8beta1-NPNT interaction in the regulation of gene expression in the intestinal mesenchyme compartment. Furthermore, the expression of NPNT has been found by qPCR to be up-regulated as much as 72-fold in human colon cancers.
CONCLUSION: These results show for the first time that NPNT is expressed and deposited by the colonic epithelium and that the interaction of NPNT with the integrin alpha8beta1 could be a key regulator of intestinal cell functions.