@Article{096504016X14813899000565,
AUTHOR = {Paweena Dana, Ryusho Kariya, KulthidaVaeteewoottacharn, Kanlayanee Sawanyawisuth, 
Wunchana Seubwai, Kouki Matsuda, Seiji Okada, Sopit Wongkham},
TITLE = {Upregulation of CD147 Promotes Metastasis of Cholangiocarcinoma  by Modulating the Epithelial-to-Mesenchymal Transitional Process},
JOURNAL = {Oncology Research},
VOLUME = {25},
YEAR = {2017},
NUMBER = {7},
PAGES = {1047--1059},
URL = {http://www.techscience.com/or/v25n7/56887},
ISSN = {1555-3906},
ABSTRACT = {CD147 is a transmembrane protein that can induce the expression and activity of matrix metalloproteinases 
(MMPs). Expression of CD147 has been shown to potentiate cell migration, invasion, and metastasis of 
cancer. In this study, the critical role of CD147 in metastasis was elucidated using CD147-overexpressing 
cholangiocarcinoma (CCA) cells in vitro and in vivo. The molecular mechanism, demonstrated herein, supported the hypothesis that metastasis increased in CD147-overexpressing cells. Five CD147-overexpressing 
clones (Ex-CD147) were established from a low CD147-expressing CCA cell line, KKU-055, using lentivirus containing pReceiver-Lenti-CD147. The metastatic capability was determined using the tail vein injection mouse model and an in vitro 3D invasion assay. Liver colonization was assessed using anti-HLA class I 
immunohistochemistry. Adhesion abilities, cytoskeletal arrangements, MMP activities, the expressions of 
adhesion molecules, and epithelial–mesenchymal transitional markers were analyzed. All Ex-CD147 clones 
exhibited a high CD147 expression and high liver colonization in the tail vein-injected mouse model, whereas 
parental cells lacked this ability. Ex-CD147 clones exhibited metastatic phenotypes (i.e., an increase in 
F-actin rearrangement) and cell invasion and a decrease in cell adhesion. The molecular mechanisms were 
shown to be via the induction of MMP-2 activity and enhancement of epithelial–mesenchymal transitions. 
An increase in mesenchymal markers Slug, vimentin, and N-cadherin, and a decrease in epithelial markers 
E-cadherin and claudin-1, together with suppression of the adhesion molecule ICAM-1, were observed in 
the Ex-CD147 clones. Moreover, suppression of CD147 expression using siCD147 in two CCA cell lines 
with high CD147 expression significantly decreased cell migration and invasion of these CCA cells. These 
findings emphasize the essential role of CD147 in CCA metastasis and suggest CD147 as a promising target 
for the effective treatment of CCA.},
DOI = {10.3727/096504016X14813899000565}
}