Enhanced Expression of Trophinin Promotes Invasive and Metastatic Potential of Human Gallbladder Cancer Cells

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2008 Oct 11

PMID 18846386

Citations 9

Authors

Xin-Zhong Chang

Jie Yu

Xue-Hui Zhang

Jian Yin

Tao Wang

Xu-Chen Cao

Affiliations

Soon will be listed here.

Abstract

Purpose: To study effects of trophinin on the metastatic potential of human gallbladder cancer cells and its potential mechanism.

Materials And Methods: Expression of trophinin in the highly metastatic GBC-SDH(i) cells was investigated by real time RT-PCR and western blot. Recombinant expression plasmid vector of the human trophinin gene was constructed and transfected into GBC-SD cells. Effects of trophinin on the invasion of GBC-SD cells were investigated by adhesion assay and invasion assay in vitro. The siRNA was used to down-regulate the expression of trophinin. Some genes related to the invasion and metastasis of cancer were determined by real time RT-PCR and western blot. The pulmonary metastasis regulated by trophinin was determined in the nude mice.

Results: Overexpression of trophinin in GBC-SDH(i) cells was confirmed compared with its parental counterparts. Up-regulation of trophinin enhanced the in vitro invasion in the GBC-SD/TRO cells. The enhancement was associated with increasing integrin alpha3, MMP-7, MMP-9, and Ets-1 expression. The results were further demonstrated by RNA interference experiment in vitro. In in vivo study, we also demonstrated that trophinin-transfected gallbladder cancer cells had more pulmonary metastases than the vector-transfected one or its parental counterparts.

Conclusion: Overexpression of trophinin leads to a more invasive phenotype and metastatic potential in human gallbladder cancer, at least in part, through regulating integrin alpha3, MMP-7, MMP-9, and Ets-1 expression.

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