M Jordinson1, I El-Hariry, D Calnan, J Calam, M Pignatelli. 1. Division of Investigative Science, Imperial College of Science, Technology, and Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
Abstract
BACKGROUND: Dietary lectins can alter the proliferation of colonic cells. Differentiation is regulated by adhesion molecules which, being glycosylated, are targets for lectin binding. AIMS: To examine the effects of dietary lectins on differentiation, adhesion, and proliferation of colorectal cancer cells. METHODS: Differentiation was assessed in three dimensional gels, adhesion by aggregation assay, and proliferation by 3H thymidine incorporation. The role of the epithelial cell adhesion molecule (epCAM) was studied using a specific monoclonal antibody in blocking studies and Western blots. The human colon cancer cell lines LS174T, SW1222, and HT29 were studied. RESULTS: The cell line LS174T differentiated in the presence of Vicia faba agglutinin (VFA) into gland like structures. This was inhibited by anti-epCAM monoclonal antibody. Expression of epCAM itself was unaffected. VFA as well as wheat germ agglutinin (WGA) and the edible mushroom lectin (Agaricus bisporus lectin, ABL) significantly aggregated LS174T cells but peanut agglutinin (PNA) and soybean agglutinin (SBA) did not. All lectins aggregated SW1222 and HT29 cells. Aggregation was blocked by the corresponding sugars. Aggregation of cells by VFA was also inhibited by anti-epCAM. VFA, ABL, and WGL inhibited proliferation of all the cell lines; PNA stimulated proliferation of HT29 and SW1222 cells. In competition studies all sugars blocked aggregation and proliferation of all cell lines, except that the addition of mannose alone inhibited proliferation. CONCLUSION: VFA stimulated an undifferentiated colon cancer cell line to differentiate into gland like structures. The adhesion molecule epCAM is involved in this. Dietary or therapeutic VFA may slow progression of colon cancer.
BACKGROUND: Dietary lectins can alter the proliferation of colonic cells. Differentiation is regulated by adhesion molecules which, being glycosylated, are targets for lectin binding. AIMS: To examine the effects of dietary lectins on differentiation, adhesion, and proliferation of colorectal cancer cells. METHODS: Differentiation was assessed in three dimensional gels, adhesion by aggregation assay, and proliferation by 3H thymidine incorporation. The role of the epithelial cell adhesion molecule (epCAM) was studied using a specific monoclonal antibody in blocking studies and Western blots. The humancolon cancer cell lines LS174T, SW1222, and HT29 were studied. RESULTS: The cell line LS174T differentiated in the presence of Vicia faba agglutinin (VFA) into gland like structures. This was inhibited by anti-epCAM monoclonal antibody. Expression of epCAM itself was unaffected. VFA as well as wheat germ agglutinin (WGA) and the edible mushroom lectin (Agaricus bisporus lectin, ABL) significantly aggregated LS174T cells but peanut agglutinin (PNA) and soybean agglutinin (SBA) did not. All lectins aggregated SW1222 and HT29 cells. Aggregation was blocked by the corresponding sugars. Aggregation of cells by VFA was also inhibited by anti-epCAM. VFA, ABL, and WGL inhibited proliferation of all the cell lines; PNA stimulated proliferation of HT29 and SW1222 cells. In competition studies all sugars blocked aggregation and proliferation of all cell lines, except that the addition of mannose alone inhibited proliferation. CONCLUSION: VFA stimulated an undifferentiated colon cancer cell line to differentiate into gland like structures. The adhesion molecule epCAM is involved in this. Dietary or therapeutic VFA may slow progression of colon cancer.
Authors: P Went; M Vasei; L Bubendorf; L Terracciano; L Tornillo; U Riede; J Kononen; R Simon; G Sauter; P A Baeuerle Journal: Br J Cancer Date: 2006-01-16 Impact factor: 7.640