Loss of co-localization of alpha 6 beta 4 integrin and collagen VII in bladder cancer.

In normal epithelial cells, the alpha 6 beta 4 integrin co-localizes with the hemidesmosomal anchoring complex on the basolateral surface of basal cells. We studied the co-expression of alpha 6 beta 4 integrin with collagen VII, a component of the hemidesmosomal anchoring complex, in normal bladder tissues and in bladder cancers. In normal bladder, the alpha 6 beta 4 integrin co-localized with collagen VII at the junction of the basolateral surface of the basal urothelial cells and the lamina propria. In five of six noninvasive bladder cancers, the localization of collagen VII remained unchanged, found at the junction of the basal cells and the papillary connective tissue. However, in these tumors the alpha 6 beta 4 expression was not polarized and was expressed on suprabasal as well as basal cells. In invasive bladder cancers, the majority (25 of 30) showed either loss of alpha 6 beta 4 and/or collagen VII expression or showed a lack of co-localization of alpha 6 beta 4 and collagen VII. Our results show derangement of the co-localization of these two components of the hemidesmosomal anchoring complex is a consistent event in bladder cancer. Furthermore, the degree of derangement increases in invasive cancers. Loss of co-expression and co-localization of alpha 6 beta 4 and collagen VII may predispose cancer cells to local invasion and may facilitate metastasis as well.