Effect of brefeldin A on membrane localization of MUC1 mucin and adhesive properties of cancer cells
Abstract:
Transmembrane glycoproteins play a significant role in cancer cells adhesion and metastatic process, just for that reason the glycosylation inhibitors are used to change the glycan structure and in this way the membrane expression of glycoproteins. The inhibitory effect of brefeldin A (BFA) on the expression of some glycoproteins: MUC1 mucin and α2β1 integrin on cell surface of breast (MCF-7 and MDA-MB-231 lines) and endometrial (Ishikawa line) cancer cells was evaluated in our study. In MCF-7 and MDA-MB-231 cells, a decrease in MUC1 expression depended on brefeldin A concentration and equaled about 40% in cells treated with 1mg% of drug. In Ishikawa cells, a decrease in MUC1 expression was lower and amounted to about 25%. The expression of α2β1 integrin was greatly inhibited in brefeldin-treated MCF-7 and Ishikawa cells, though it was unchanged in MDA-MB-231 cells. A decrease in MUC1 mucin and α2β1 integrin level reduced the adhesive properties of BFA-treated cells. Adhesion to type I collagen was greatly diminished in BFA-treated MCF-7 and Ishikawa cells (above 70%), and to a lesser degree in MDA-MB-231 cells (about 50%); which was mainly caused by the inhibited integrin expression. These findings have proved that brefeldin A, by changing the surface glycoproteins level, can alter carcinoma cells adhesion to extracellular matrix proteins.