Role of the implantation-related cell adhesion molecule, trophinin in progression of colorectal cancer.

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Trophinin is a cell adhesion molecule expressed by both trophoblasts and maternal cells, where it is implicated in human embryo implantation through a homophilic mechanism. During the process of implantation, trophoblasts aggressively invade and actively proliferate to form the placenta, a process resembling tumor invasion. In the research project, we first identify human chorionic gonadotrophin (hCG) as a stimulator of trophinin, We then demonstrate that trophinin is expressed in colorectal cancer cells in 59.5% of 42 patients examined, and that its expression is closely associated with poor prognosis. Expression of human chorionic gonadotrophin was associated with trophinin expression in these patients. To determine whether trophinin enhances invasion of cancer cells, colon adenocarcinoma SW480-tro cells stably expressing trophinin were established by transfection, and Matrigel assays showed that these cells were more invasive than mock-transfected cells. A microarray search for transcripts up-regulated in SW480 cells transiently transfected by trophinin cDNA identified the high-mobility group box 1 gene (HMGB1). In addition, the receptor for advanced glycation end products (RAGE), which serves as a ligand of HMGB1, was largely co-expressed with trophinin in colorectal cancer tissue specimens. These results suggest that trophinin enhances cancer cell invasiveness through a mechanism involving HMGB1/RAGE and that its expression indicates a poor prognosis in colorectal cancer.