HOME
Return to Table of Contents
LUTHERAN GLYCOPROTEIN VARIANTS SLOW PROLIFERATION OF CACO 2/15 CELLS
IC Teller1, E Herring1, SF Parsons2, J-F Beaulieu1, CIHR Group in Functional Development and Physiopathology of the Digestive Tract
1Département d’anatomie et de biologie cellulaire, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec; 2International Blood Group Reference Laboratory, Bristol Institute for Transfusion Sciences, Bristol, UK
Lutheran glycoproteins (Lu gps) are specific receptors for laminin (LM)-511/521. The two receptors known as LU and LU(v13), also known as BCAM are overexpressed in certain epithelial cancers. Little is known of Lu gp expression and function in the intestinal epithelium or colorectal cancer. In this study, we have determined the localization of both Lu gps in the fetal and adult gut as well as in enterocyte-like Caco-2/15 cells cultured on stromal cells. Isolated fractions of epithelium and stroma were generated and expression levels investigated. We then examined the expression of Lu gps in colorectal cancer samples at both the protein and transcript levels. In addition, overexpression of both variants was forced in the Caco 2/15 cell line. The variant function was then investigated by growth curves and BrdU incorporation assays (BrdU-IA). Indirect immuno-fluorescence (IF) illustrates the presence of Lu gps in the fetal epithelium, and disappearance in the adult. Lu gp transcript levels disappear from isolated adult epithelium as well as LM-511. This LM is still present in the adult basement membrane (BM), because we show here that it is deposited only by stromal cells. IF on colon carcinoma samples were negative for Lu gps in the surface epithelium in most, but not all samples. Coculture of Caco-2/15 with stroma cells revealed expression of Lu gps at the cell base and lateral membrane indicating a possible function in cell-cell interaction. Growth curves were performed on overexpressing Caco 2/15 cells counting after 3, 5, and 7 days. LU and LU(v13) slowed proliferation by 50 and 85%, respectively compared to empty vector (EV) cells. BrdU-IA confirmed these results. Taken together our data suggest a role for Lu gps in development that involves inhibition of cell proliferation.