Elevated expression of Cyr61 enhances peritoneal dissemination of gastric cancer cells through integrin α2β1
Journal
Journal of Biological Chemistry
Journal Volume
282
Journal Issue
47
Pages
34594-34604
Date Issued
2007
Author(s)
Abstract
Cysteine-rich 61 (Cyr61/CCN1) is involved in human gastric cancer development and progression. Nonetheless, the role of Cyr61 as regards peritoneal dissemination of such cancers has not yet been completely characterized. We used liposome-mediated transfection to establish Cyr61, or antisense Cyr61, expression vectors into gastric cancer AGS or MKN45 cell lines. Transfectants were tested by means of a cancer-cell adhesion assay in vitro and ex vivo. Furthermore, a functional integrin fluorescence-activated cell sorting assay, reverse transcription-PCR, and an AP-1 reporter assay were performed to investigate the potential signaling pathway of Cyr61. It was shown that stable transfection of Cyr61 into the AGS cell line strongly enhanced its adhesion ability. The overexpression of Cyr61 within AGS cells significantly increased the functional expression of integrin α2β1. Function-neutralizing antibody to integrin α2β1 effectively suppressed the Cyr61-mediated enhanced adhesion of AGS cells to peritoneal tissue. Promoter assays of integrin α2 gene further revealed that the AP-1 pathway was evidently activated within Cyr61-expressing AGS cells. Animal studies have revealed that mice injected with Cyr61-overexpressed AGS cells featured a greater number of peritoneal seeding nodules and a lower survival rate than the Neo control cell lines, and when such cells were treated with functional blocking antibody to integrin α2β 1, they were able to elicit a decline in the peritoneal dissemination. The data suggest that Cyr61 may contribute to the peritoneal dissemination of gastric cancer by promoting tumor-cell adhesion ability through the up-regulation of the functional integrin α2β 1 via an AP-1-dependent pathway. ? 2007 by The American Society for Biochemistry and Molecular Biology, Inc.
SDGs
Other Subjects
Antibodies; Cell adhesion; Cells; Fluorescence; Tissue; Transcription; Expression vectors; Gastric cancer; Peritoneal tissue; Tumor cell adhesion; Oncology; alpha2 integrin; blocking antibody; cysteine rich protein 61; liposome; neutralizing antibody; transcription factor AP 1; very late activation antigen 2; animal tissue; article; cancer cell; cell adhesion; cell selection; cell survival; controlled study; ex vivo study; female; gene control; genetic transfection; human; human cell; immunohistochemistry; in vitro study; mouse; nonhuman; peritoneum; peritoneum metastasis; priority journal; protein expression; protein phosphorylation; reverse transcription polymerase chain reaction; SCID mouse; stomach cancer; Animals; Antibodies; Cell Adhesion; Cell Line, Tumor; DNA, Antisense; Gene Expression Regulation, Neoplastic; Humans; Immediate-Early Proteins; Integrin alpha2beta1; Intercellular Signaling Peptides and Proteins; Liposomes; Mice; Mice, SCID; Neoplasm Transplantation; Peritoneal Neoplasms; Peritoneum; Promoter Regions (Genetics); Signal Transduction; Stomach Neoplasms; Transcription Factor AP-1; Transfection; Up-Regulation; Animalia; Mus
Type
journal article