Morphoregulatory activities of E-cadherin and beta-1 integrins in colorectal tumour cells

Abstract

The cadherin family of adhesion molecules are prime mediators of cell-cell interactions while the integrins predominantly mediate cell-matrix and to a lesser extent cell-cell binding specificity. We have recently shown that a human colon carcinoma cell line (SW1222) organizes into glandular structures, with well defined polarity when cultured in three-dimensional type I collagen gel. The current study indicates that SW1222 cells display high levels of E-cadherin (E-cd, epithelial cadherin) by western blotting and immunohistochemical staining. A monoclonal antibody (HECD-1) specific for human E-cd blocks cell-cell adhesion (100%) and inhibits (up to 75%) the glandular differentiation of SW1222 cells growing in collagen gel. Furthermore the anti-beta 1 integrin monoclonal antibody (mAb13) inhibits the glandular differentiation of SW1222 cells (61%) and their cellular binding to type I collagen (60%). However, no significant inhibition of cell-cell adhesion was demonstrated using mAb13 nor the anti-carcinoembryonic antigen monoclonal antibody (PR3B10). These results are consistent with E-cd being a cell-cell adhesion molecule expressed by SW1222 cells. These data indicate that E-cd and beta 1 integrins mediate cell-cell and cell-collagen interactions required for the induction and maintenance of the glandular differentiation of colorectal tumour cells. Thus the down-regulation or loss of E-cd and beta 1 integrins seen in poorly differentiated colorectal tumours may represent one of the abnormalities underlying their progression towards an undifferentiated phenotype in vivo.