DIMINISHED EXPRESSION OF INTEGRIN ADHESION MOLECULES ON HUMAN COLONIC EPITHELIAL-CELLS DURING THE BENIGN TO MALIGN TUMOR TRANSFORMATION

Integrins are transmembrane molecules that mediate cell-cell and cell-substratum adhesion. Because alterations in the adhesive properties of tumour cells are thought to influence tumour cell invasion, the expression of integrin-alpha and beta-chains in 19 human colorectal carcinomas, eight adenomas, and eight normal colon tissues was examined immunohistochemically using an indirect immunofluorescent technique. Normal colonic epithelial cells were found to express the integrin alpha(3), alpha(5), alpha(6), beta(1), and beta(4) chains, whereas the alpha(2) chain was expressed only on epithelial cells lining the base of the crypts and was absent from cells lining the mouth of the crypts or the surface epithelium. No epithelial staining of the alpha(1), alpha(4), beta(2), and beta(3) chains was observed. A progressive reduction of all normally expressed alpha and beta-chains was associated with increasing neoplastic transformation. The expression of the alpha(3) and alpha(5) chains was already noticeably reduced in adenomas, and was completely absent in most colonic carcinomas. In contrast, alpha(6), beta(1), and beta(4) expression was maintained in adenomas, whereas the transformation from benign to malignant neoplasms associated with infiltrative growth was characterised by diminished or lost expression of alpha(6), beta(1), and beta(4) chains. Thus, the decreased expression of integrins in human colon carcinomas may contribute to the altered adhesion and migration properties of these tumour cells.