MODELS OF COLORECTAL TUMOR DIFFERENTIATION

In vitro models in which colorectal tumour cells express differentiate d and undifferentiated phenotypes have been developed and used to iden tify the molecular mechanisms of cellular and morphological differenti ation of colorectal epithelial cells. Our data indicate that both cell -cell and cell-collagen interactions are required for the induction an d maintenance of the glandular differentiation of colon carcinoma cell lines in vitro. These interactions are primarily mediated by two clas ses of adhesion molecules, E-cadherin and alpha 2/beta 1 integrin. Bot h cell surface adhesion receptors are lost in poorly differentiated co lorectal tumours, and these changes may explain in part the phenotype and behaviour in vivo. Further investigation of the molecular control of integrin and cadherin function, localization and level of cell surf ace expression will constitute the basis of new functional assessment of tumour differentiation and likely response to treatment in colorect al cancer.