z-logo
Premium
Identification of CXCL5/ENA‐78 as a factor involved in the interaction between cholangiocarcinoma cells and cancer‐associated fibroblasts
Author(s) -
Okabe Hirohisa,
Beppu Toru,
Ueda Mitsuharu,
Hayashi Hiromitsu,
Ishiko Takatoshi,
Masuda Toshiro,
Otao Ryu,
Horlad Hasita,
Mima Kosuke,
Miyake Keisuke,
Iwatsuki Masaaki,
Baba Yoshifumi,
Takamori Hiroshi,
Jono Hirofumi,
Shinriki Satoru,
Ando Yukio,
Baba Hideo
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27496
Subject(s) - cxcl5 , stromal cell , hepatic stellate cell , cancer research , intrahepatic cholangiocarcinoma , autocrine signalling , tumor microenvironment , cancer cell , immunotoxin , receptor , biology , pathology , medicine , cancer , immunology , tumor cells , monoclonal antibody , antibody , chemokine
Abstract Knowledge of tumor‐stromal interactions is essential for understanding tumor development. We focused on the interaction between cholangiocarcinoma and cancer‐associated fibroblasts (CAFs) in intrahepatic cholangiocarcinoma and reported their positive interaction in vitro and in vivo . The aim of this study is to identify the key protein involved in the interaction between cholangiocarcinoma cells and CAFs and its role on cholangiocarcinoma progression. Using the conditioning medium from cholangiocarcinoma cells, hepatic stellate cells and coculture of them, Protein‐Chip analysis with SELDI–TOF–MS showed that the peak of an 8,360‐Da protein remarkably increased in the coculture medium. This protein was identified as CXCL5/ENA78, epithelial cell‐derived neutrophil‐activating peptide‐78, by q‐TOF/MS/MS analysis. Two cholangiocarcinoma cell lines, HuCCT1 and RBE, produced CXCL5 that promoted their invasion and migration in an autocrine fashion. These effects of CXCL5 significantly decreased by inhibition of CXC‐receptor 2, which is the receptor for CXCL5. In addition, IL‐1β produced by hepatic stellate cells induced the expression of CXCL5 in cholangiocarcinoma cells. In human tissue samples, a significant correlation was observed between CAFs and CXCL5 produced by cholangiocarcinoma cells in intrahepatic cholangiocarcinoma ( p = 0.0044). Furthermore, the high‐CXCL5‐expression group exhibited poor overall survival after curative hepatic resection ( p = 0.027). The presence of tumor‐infiltrating neutrophils expressing CD66b was associated with CXCL5 expression in tumor cells ( p < 0.0001). These data suggest that CXCL5 is important for the interaction between cholangiocarcinoma and CAFs, and inhibition of tumor‐stromal interactions may be a useful therapeutic approach for cholangiocarcinoma.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here