Role of integrin α1 subunits in gastric cancer patients with peritoneal dissemination

Abstract

The interaction between gastric cancer (GC) cells and the peritoneum is a critical event in peritoneal dissemination. The molecular mechanisms of this dissemination, however, remain unclear. Integrins are heterodimeric cell adhesion molecules consisting of α and β subunits that serve as adhesion receptors for extracellular matrix proteins and cellular ligands, and may participate in GC peritoneal dissemination. In this study, we isolated fresh GC cells from a patient with peritoneal metastasis and examined them for integrin expression and investigated the role of integrin α1 subunit molecules in GC. Five clones (KGC1C2, KGC1F3, KGC1H3, KGC1E8, KGC1G10) were established from the clinical GC sample and used in an in vitro adhesion model using a single cell culture method. Each clone was transplanted into the peritoneal cavity of SCID mice, where each clone formed tumors and caused conglutination of organs in the abdominal cavity. We analyzed the expression of integrin subunits for each clone by flow cytometry and found that the expression ratio of α1 subunits paired with β1 subunits was detected at higher levels than other subunits. To verify that anti-integrin α1 subunit (CD49a) antibody inhibits cell adhesion in an in vitro adhesion assay, each clone was treated with anti-CD49a antibody, which significantly inhibited cell adhesion compared to the untreated group. Characterization of α1 subunit expression in GC may be useful in optimizing treatments for different individuals. Having high metastatic abilities, these 5 new GC clones may be beneficial for analyzing integrin function in tumor metastasis.