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

滋养素是一种由滋养细胞和母细胞共同表达的细胞粘附分子，通过嗜同性机制参与人胚胎着床。在着床过程中，滋养细胞积极侵袭并积极增殖形成胎盘，这一过程类似于肿瘤侵袭。在本研究项目中，我们首先确定了人绒毛膜促性腺激素（hCG）作为营养素的刺激因子，然后我们证明了42例被检查的患者中有59.5%的人在结直肠癌细胞中表达营养素，并且其表达与不良预后密切相关。在这些患者中，人绒毛膜促性腺激素的表达与滋养素的表达相关。为了确定滋养素是否能增强癌细胞的侵袭性，我们转染了稳定表达滋养素的结肠癌腺癌SW480-tro细胞，Matrigel实验显示这些细胞比模拟转染的细胞更具侵袭性。通过微阵列搜索瞬时转染营养素cDNA的SW480细胞中上调的转录本，发现了高迁移率的组框1基因（HMGB1）。此外，晚期糖基化终产物受体（RAGE）作为HMGB1的配体，在结直肠癌组织标本中与营养素大量共表达。这些结果表明，营养素通过HMGB1/RAGE参与的机制增强了癌细胞的侵袭性，其表达提示结直肠癌预后不良。

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.