The role of trophinin, an adhesion molecule unique to human trophoblasts, in progression of colorectal cancer

Abstract

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 5 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 trophininexpressing 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 5 32). These results suggest that trophinin promotes invasion through a mechanism involving HMGB1/ RAGE. ' 2007 Wiley-Liss, Inc.

Trophinin-mediated cell adhesion induces apoptosis of human endometrial epithelial cells through PKC-δ

“…In testicular and colon cancer, trophinin expression is associated with invasive activity of tumor cells. [23][24][25] In the invasive trophoblast, interactions of trophinin with cytoplasmic signaling molecules may differ from those in silent trophectoderm cells described our previous study in reference 9, or from those occurring in endometrial epithelial cells described here.…”

A Pathway for the Control of Anoikis Sensitivity by E-Cadherin and Epithelial-to-Mesenchymal Transition

“…In this connection, our results suggest that NRAGE is potentially oncogenic and/or prometastatic. Intriguingly, a prometastatic role of the related MAGE-D3/trophinin gene in colorectal carcinoma (38) has been shown previously. In apparent contradiction, NRAGE inhibited metastasis in a pancreatic cancer cell line and a growth-arrested a breast cancer cell line, but the highlevel adenoviral expression used in those studies may have produced nonphysiologic effects (16,21).…”

“…The related protein MAGE-A3 supports melanoma cell survival and is overexpressed in lung cancer, correlating with poor prognosis (36,102). The NRAGE orthologue trophinin/MAGE-D3 is overexpressed in colorectal carcinoma, where it promotes tumor metastasis (38). Thus, although NRAGE is proapoptotic with respect to the p75 and Unc5 receptors, paradoxical protumorigenic functions of the protein have not yet been explored.…”

Trophinin: What embryo implantation teaches us about human cancer.

“…43,44 In this review, any type of epithelial cancers in men and women producing hCG are considered trophoblastic cancer and discussed below for their relation to embryo implantation, as hCG and trophinin are closely linked in human cancers. [45][46][47] Many human endometrial adenocarcinoma lines are available, 48 whereas no mouse endometrial adenocarcinoma line has been established. This evidence may be related to the fact that no endometrial adenocarcinoma occurs in the mouse.…”