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052 THE INTEGRIN alpha8beta1 NEPHRONECTIN INTERACTION IS INVOLVED IN HUMAN COLON CANCER PROGRESSION Y Benoit, I Teller, E Herring, JF Beaulieu* 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. Moreover, it has been shown in mice that NPNT is over-expressed by some primary tumours having strong metastatic potential compared to those of low metastatic potential. These data suggest a role for the alpha8beta1 NPNT interaction in cancer progression.
Groupe IRSC sur le développement fonctionnel et la physiopathologie du tube digestif, Département d'anatomie et biologie cellulaire, Faculté de médecine et des sciences de la santé, Université de Sherbrooke
The object of our work was to characterize alpha8beta1 NPNT in human colorectal cancers and to study the role of this interaction in the progression of cancer. By Western blot and RT-PCR, we have shown that NPNT, normally expressed in small amounts by colonocytes, is strongly produced and deposited at the basement membrane of the cancer cell line, Caco-2/15. Furthermore, the expression of NPNT has been found by QPCR to be as much as 72-fold up-regulated in certain cases of human colon cancer. By semi-quantitative RT-PCR, we have established a correlation between the alpha8beta1 NPNT interaction and colorectal tumour progression.
These results show for the first time that NPNT is expressed and deposited by the colon epithelium and that the interaction of NPNT with the integrin alpha8beta1 could be a key regulator of human colon cancer progression.