title: 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.
abstract: We studied the expression and distribution of different laminin chains, the alpha 6 beta 4 integrin and type VII collagen, i.e., components of the epithelial adhesion complex, in gastric carcinomas and in suggested 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 interface between malignant cells and tumor stroma. The reactivities were continuous throughout the carcinomas, even in structures invading through the smooth muscle layers of the gastric wall. The expression of different laminin chains was accompanied by strong polarized reactivity for the alpha 6 beta 4 integrin, which is a receptor for both laminin-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 gastric epithelium showed a similar expression pattern of laminins and the alpha 6 beta 4 integrin as the gastric carcinomas. Our results suggest that gastric carcinomas use the alpha 6 beta 4 integrin and newly deposited laminin-1 and -5, accompanied by the disappearance of type VII collagen, as their mechanism of adhesion during the invasion through surrounding tissues. Unlike in previous studies, the reactivity for the laminin-5 protein was not restricted to the invading cells but surrounded the malignant glandular structures throughout the tumor. Our results also show that both intestinal-type gastric carcinoma, and intestinal metaplasia mimic the gastric surface epithelium in the expression pattern of laminins and the beta 4 integrin subunit. This supports previous studies proposing a pathogenetic sequence from intestinal metaplasia to gastric carcinoma.
authors.affiliation: Department of Anatomy, University of Helsinki, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Tani
authors.forename: T
authors.initials: T
authors.lastname: Karttunen
authors.forename: T
authors.initials: T
authors.lastname: Kiviluoto
authors.forename: E
authors.initials: E
authors.lastname: Kivilaakso
authors.forename: R E
authors.initials: RE
authors.lastname: Burgeson
authors.forename: P
authors.initials: P
authors.lastname: Sipponen
authors.forename: I
authors.initials: I
authors.lastname: Virtanen
mesh_terms: D000954:Antigens, Surface / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D003094:Collagen / Q000096:biosynthesis*; D004848:Epithelium / Q000737:chemistry; D005757:Gastritis, Atrophic / Q000473:pathology; D006801:Humans; D039161:Integrin alpha6beta4; D016023:Integrins / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D007797:Laminin / Q000096:biosynthesis*; D008679:Metaplasia / Q000378:metabolism / Q000473:pathology; D009130:Muscle, Smooth / Q000473:pathology; D009361:Neoplasm Invasiveness; D010641:Phenotype; D013270:Stomach / Q000737:chemistry; D013274:Stomach Neoplasms / Q000473:pathology / Q000503:physiopathology*; D000097794:Kalinin
chemical_list: D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D003094:Collagen; D039161:Integrin alpha6beta4; D016023:Integrins; D007797:Laminin; D000097794:Kalinin