INHIBITION OF GROWTH AND ENHANCEMENT OF DIFFERENTIATION OF COLORECTAL-CARCINOMA CELL-LINES BY MAB MR6 AND IL-4

We have previously shown that expression of gp200-MR6, a molecule that is functionally associated with the interleukin-4 receptor (IL-4R), i s lost from breast carcinoma cells as malignancy increases. Here we ha ve analysed a series of colorectal carcinoma cell lines and show a sim ilar decrease with increasing malignancy. Moreover, analysis of the HR A-19 cell line, which can exhibit a poorly or a well-differentiated ph enotype according to culture conditions, shows that gp200-MR6 is weakl y expressed on the former but strongly expressed on the latter. Functi onal analysis using either IL-4 or monoclonal antibody (MAb) MR6 and t he well-differentiated cell line SW1222 revealed that MAb MR6 acts as an agonist for IL-4, with both reagents causing a dose-dependent inhib ition of cell division, but greatly enhancing the glandular differenti ation of SW1222 in three-dimensional collagen gels. These observations suggest that the gp200-MR6 molecule may act as the product of a tumou r suppressor gene and that its loss may be a primary event in tumourig enesis. (C) 1997 Wiley-Liss, Inc.