LOSS OF COLOCALIZATION OF ALPHA-6-BETA-4 INTEGRIN AND COLLAGEN-VII INBLADDER-CANCER

In normal epithelial cells, the alpha 6 beta 4 integrin colocalizes wi th the hemidesmosomal anchoring complex on the basolateral surface of basal cells. We studied the co-expression of alpha 6 beta 4 integrin w ith 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 vn at the junct ion of the basolateral surface of the basal urothelial cells and the l amina propria. In five of six noninvasive bladder cancers, the localiz ation of collagen VII remained unchanged, found at the junction of the basal cells and the papillary connective tissue. However, in these tu mors the alpha 6 beta 4 expression was not polarized and was expressed on suprabasal as well as basal cells. In invasive bladder cancers, th e majority (25 of 30) showed either loss of alpha 6 beta 4 and/or coll agen VII expression or showed a lack of colocalization of alpha 6 beta 4 and collagen VII. Our results show derangement of the co-localizati on of these two components of the hemidesmosomal anchoring complex is a consistent event in bladder cancer. Furthermore, the degree of deran gement increases in invasive cancers. Loss of co-expression and co-loc alization of alpha 6 beta 4 and collagen VII may predispose cancer cel ls to local invasion and may facilitate metastasis as well.