ALPHA(6)BETA(4) INTEGRIN AND NEWLY DEPOSITED LAMININ-1 AND LAMININ-5 FORM THE ADHESION MECHANISM OF GASTRIC-CARCINOMA - CONTINUOUS EXPRESSION OF LAMININS BUT NOT THAT OF COLLAGEN-VII IS PRESERVED IN INVASIVE PARTS OF THE CARCINOMAS - IMPLICATIONS FOR ACQUISITION OF THE INVADING PHENOTYPE

We studied the expression and distribution of different laminin chains , the alpha(6) beta(4) integrin and type VII collagen, ie, components of the epithelial adhesion complex, in gastric carcinomas and in sugge sted preneoplastic stages of this malignancy. Intestinal-type gastric carcinomas showed strong reactivity for laminin alpha 1, alpha 3, beta 1, and beta 3 chains, the components of laminin-1 and -5, at the inte rface between malignant cells and tumor stroma. The reactivities were continuous throughout the carcinomas, even in structures invading thro ugh the smooth muscle layers of the gastric wall. The expression of di fferent laminin chains was accompanied by strong polarized reactivity for the alpha(6) beta(4) integrin, which is a receptor for both lamini n-1 and laminin-5. Collagen type VII was only occasionally present at sites showing reactivity for laminin-5 and was totally absent from the cell islands invading through the gastric wall. Intestinalized gastri c epithelium showed a similar expression pattern of laminins and the a lpha(6) beta(4) integrin as the gastric carcinomas. Our results sugges t that gastric carcinomas use the alpha(6) beta(4) integrin and newly deposited laminin-1 and -5, accompanied by the disappearance of type V II collagen, as their mechanism of adhesion during the invasion throug h surrounding tissues. Unlike in previous studies, the reactivity for the laminin-5 protein was not restricted to the invading cells but sur rounded the malignant glandular structures throughout the tumor. Our r esults also show that both intestinal-type gastric carcinoma and intes tinal metaplasia mimic the gastric surface epithelium in the expressio n pattern of laminins and the beta(4) integrin subunit. This supports previous studies proposing a pathogenetic sequence from intestinal met aplasia to gastric carcinoma.