CADM1 promotes adhesion to vascular endothelial cells and transendothelial migration in cultured GIST cells.

Abstract

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the human gastrointestinal tract. Small intestinal GISTs appear to be associated with poorer prognosis and higher metastasis rate than gastric GISTs of the same size and mitotic index. Recently, we reported that cell adhesion molecule 1 (CADM1) is expressed specifically in most small intestinal GISTs, but not in most gastric GISTs, suggesting that this difference in CADM1 expression between gastric GISTs and small intestinal GISTs might influence the difference in clinical behavior between them. The aim of the present study was to examine whether high CADM1 expression affected proliferation, migration, invasion, adhesion to endothelial cells and transendothelial migration of cultured GIST cells by comparing original GIST-T1 cells with very low CADM1 expression with GIST-T1 cells with high CADM1 expression induced by CADM1 cDNA transfection (GIST-T1-CAD cells). GIST-T1-CAD cells had reduced ability to proliferate, migrate and invade compared with the original GIST-T1 cells, but showed significantly higher ability to adhere to human umbilical vein endothelial cells and migrate through endothelial cell monolayers. Thus, CADM1 may contribute to higher metastasis rates in small intestinal GISTs facilitating tumor cell adhesion to vascular endothelial cell and transendothelial migration of tumor cells. CADM1 might serve as a potential target for inhibition of metastasis in small intestinal GISTs.