Cell-matrix interactions are thought to be of critical importance in the regulation of various cell functions, including proliferation, migration and control of gene expression. The integrins, a large family of specific receptors for the macromolecules of the extracellular matrix, are important mediators of these interactions. The integrin alpha9beta1 is one of the integrins whose expression is restricted to specialized tissues. Its exact function is unknown. In the present study, we have analyzed expression of the alpha9 subunit in human colonic epithelial cells by indirect immuno-fluorescence and Western and Northern blots. In normal intact tissues, the antigen was detected at the basolateral domain of epithelial cells in colonic glands at the fetal stage but was absent in adults. Strong staining was detected constitutively in contractile cells at both stages. In adenocarcinomas, the alpha9 subunit was detected at the basolateral domain of epithelial cells in 6 of the 10 tumors tested, while a reduction of the staining was observed in the sub-epithelial myofibroblasts in parallel with peri-glandular stroma disorganization. The potential for colon adenocarcinoma cells to express the integrin alpha9 subunit was confirmed at both the protein and transcript levels in Caco-2 and T84 cell lines, 2 well-characterized cell lines known to exhibit polarization features. The 5 other cell lines tested were negative for expression of the alpha9 subunit. Taken together, our observations suggest that the alpha9 integrin subunit is subject to an onco-fetal pattern of expression in human colonic epithelium.