Morphoregulatory activities of E-cadherin and beta-1 integrins in colorectal tumour cells.
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.
Pignatelli
M
M
Department of Histopathology, Royal Postgraduate Medical School, London, UK.
Liu
D
D
Nasim
M M
MM
Stamp
G W
GW
Hirano
S
S
Takeichi
M
M
D015153:Blotting, Western; D015820:Cadherins / Q000032:analysis / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation; D003094:Collagen / Q000502:physiology; D003110:Colonic Neoplasms / Q000737:chemistry / Q000473:pathology*; D006801:Humans; D019012:Integrin beta1; D016023:Integrins / Q000032:analysis / Q000502:physiology*; D014407:Tumor Cells, Cultured
D015820:Cadherins; D019012:Integrin beta1; D016023:Integrins; D003094:Collagen