title: Potentiation of cell invasion and matrix metalloproteinase production by alpha3beta1 integrin-mediated adhesion of gastric carcinoma cells to laminin-5.
abstract: We previously reported that the adhesion of gastric carcinoma cells to the peritoneum mediated by the alpha3beta1 integrin-laminin interaction is a key step in the initial process of peritoneal metastatic dissemination. Carcinoma cells subsequently invade through the intercellular gaps of mesothelial linings. In this study, we examined the role of the interaction of carcinoma cells with laminin-5, which is a major component of submesothelial basement membranes and serves as a high-affinity ligand for alpha3beta1 integrin, in carcinoma cell invasion. Human gastric carcinoma cell lines (MKN1, GT3TKB, and NUGC-4) adhered in an alpha3beta1 integrin-dependent manner to the extracellular matrix deposited by peritoneal mesothelial cells. An in vitro invasion assay using the Boyden chamber system revealed that MKN1 cell migration through the membranes increased when the membranes were coated with matrices produced by mesothelial cells or with laminin-5-containing Matrigel as compared to Matrigel alone. The cell migration promoted by laminin-5-containing Matrigel was inhibited by the presence of anti-alpha3 integrin antibody. When MKN1 cells were cultured in a laminin-5-coated plate, these cells were promoted to produce matrix metalloproteinase (MMP)-9, as assessed by gelatin zymography, enzyme-linked immunosorbent assay, and reverse transcription-polymerase chain reaction. These results suggest that the production of MMP-9 by MKN1 cells was potentiated by the alpha3beta1 integrin-laminin-5 interaction, which facilitated their invasion via degradation of the matrix.
authors.affiliation: Department of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Saito
authors.forename: Wakana
authors.initials: W
authors.lastname: Sekine
authors.forename: Rikio
authors.initials: R
authors.lastname: Sano
authors.forename: Shinya
authors.initials: S
authors.lastname: Komatsu
authors.forename: Hiromi
authors.initials: H
authors.lastname: Mizuno
authors.forename: Kouji
authors.initials: K
authors.lastname: Katabami
authors.forename: Kentaro
authors.initials: K
authors.lastname: Shimada
authors.forename: Teruaki
authors.initials: T
authors.lastname: Oku
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tsuji
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D039201:Integrin alpha3beta1 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D000097794:Kalinin
chemical_list: D015815:Cell Adhesion Molecules; D039201:Integrin alpha3beta1; D020780:Matrix Metalloproteinase 9; D012333:RNA, Messenger; D000097794:Kalinin