Trophinin is a unique adhesion molecule expressed by human trophoblastic cells. Its activity and in vivo expression pattern implicate trophinin in the initial attachment of trophectoderm cells to maternal epithelia. Subsequent to apical adhesion, trophoblasts aggressively invade maternal tissue to form the placenta, a process resembling tumor invasion. Here, we report that trophinin is expressed in tumors from 64% of colon cancer patients (n = 50) and high trophinin expression is closely associated with poor prognosis. To determine the link between trophinin expression and malignancy, colon adenocarcinoma SW480 cells were stably transfected with trophinin. An invasion assay showed that trophinin-expressing SW480 cells were more invasive than mock-transfected cells. Microarray analysis comparing SW480 cells transfected with trophinin with mock-transfected cells identified high-mobility group box 1 (HMGB1) as the most significantly elevated transcript. Immunohistochemical analysis of tumors from the colorectal cancer patients confirmed positive correlation of HMGB1 protein expression in the nucleus to trophinin expression in tumor. HMGB1 and its ligand RAGE (the receptor for advanced glycation end product) proteins were coexpressed in 65.6% of trophinin-positive patients (n = 32). These results suggest that trophinin promotes invasion through a mechanism involving HMGB1/RAGE.
(c) 2007 Wiley-Liss, Inc.