No abstract

Intercellular adhesion molecule-1 (ICAM-1) is a cell surface adhesion glycoprotein that mediates leukocyte adhesion through interaction with the leukocyte CD11/CD18 adhesion complex. The aim of this study was to determine whether ICAM-1 is expressed by normal or neoplastic colonic epithelial cells. Immunohistochemical studies on human colonic tissue demonstrated focal ICAM-1 expression by colonic carcinomas but not by normal colonic epithelium. ICAM-1 expression by colonic carcinomas showed a positive correlation with the presence of a peritumoral inflammatory infiltrate. Surface expression of ICAM-1 was also observed in HT-29 cultured human colon cancer cells by both immunohistochemistry and enzyme immunoassay. Interferon-gamma and interleukin-1 beta significantly increased ICAM-1 surface expression by HT-29 cells in a dose-dependent manner. Upregulation of ICAM-1 surface expression became evident some hours after cytokine stimulation and was inhibited by both actinomycin D and cycloheximide, indicating a requirement for de novo RNA and protein synthesis. HT-29 monolayers supported adhesion of human lymphocytes as determined by a quantitative 111In-labeled leukocyte adhesion assay. Adhesion was mediated in part via interaction of ICAM-1 on HT-29 cells with lymphocyte function-associated antigen-1 (CD11a/CD18) on lymphocytes, as defined by using blocking monoclonal antibodies. Expression of ICAM-1 and/or other leukocyte adhesion receptors by neoplastic epithelial cells may play a role in directing leukocyte trafficking and leukocyte-epithelial cell interactions in colonic carcinoma.

Background Decision aids for colorectal cancer (CRC) screening have been shown to enable patients to identify a preferred screening option, but the extent to which such tools facilitate shared decision making (SDM) from the perspective of the provider is less well established.

The extent to which the insulin-like growth factor (IGF) system contributes to the initiation and progression of colon cancer remains poorly defined. We recently reported that a majority of human colon cancers express and secrete the potent mitogen IGF-II and at least two inhibitory binding proteins, IGFBP-2 and IGFBP-4. In the present study we measured the expression and secretion of IGF-II, IGFBP-2, and IGFBP-4 in relation to growth and differentiation of CaCo2 human colon cancer cells, which undergo spontaneous enterocytic differentiation in culture. Under the conditions of the present study, CaCo2 cells demonstrated an initial rapid phase of growth between Day 2 through days 7-9 of culture, followed by a significant retardation in the growth between days 9-13. Alkaline phosphatase (ALP) activity, a marker of enterocytic differentiation, progressively increased between Days 7-13 in culture, temporally correlating with post-confluent phase of negligible growth. These changes in growth and differentiation were accompanied by > 80% decline in the relative concentration of IGF-II messenger RNA (mRNA) between Days 2-13. In contrast, the relative mRNA concentrations of inhibitory binding proteins (IGFBP-2 and IGFBP-4) increased rapidly to 200% of Day 2 values by Days 5-7 before returning to baseline levels by Day 13. The relative protein concentrations of the three factors measured in the conditioned media of the cells followed a pattern very similar to that measured for the mRNA levels. While the changes in the relative protein concentrations and mRNA levels of IGF-II and IGFBP-4 were statistically significant, the changes measured in the RNA and protein levels of IGFBP-2 were not, as a result of large inter experimental variations. Thus these results suggested that CaCo2 cell differentiation may require an attenuation of IGF-II effects. To confirm the latter possibility, additional studies were conducted with a specific neutralizing antibody against IGF-II. Incubation of CaCo2 cells with anti-IGF-II antibodies from Day 0 through Day 7 significantly retarded the growth of the cells and was accompanied by a significant increase in the concentration of Alkaline phosphatase activity per 10(6) cells. Recently, we reported a potent inhibitory role of IGFBP-4 in the growth of colon cancer cells. In the present studies, a possible important role of IGF-II is illustrated not only in the growth but also in the differentiation of colonic cells. Our studies thus suggest that differential expression of IGF-II and IGFBPs may be playing a critical role in both proliferation and differentiation of colonocytes.

No abstract