Document Detail

Hepatic stellate cells accelerate the malignant behavior of cholangiocarcinoma cells.
MedLine Citation:
PMID:  21042948     Owner:  NLM     Status:  In-Data-Review    
BACKGROUND: Although tumor-stromal interaction has been discussed, the role of hepatic stellate (HS) cells against cancer, especially cholangiocarcinoma (CC), has not been clarified. The aim of this study is to investigate the effect of HS cells on CC cell progression in vitro and in vivo.
METHODS: The effects of CC conditioned medium (CC-CM) on activation and proliferation of HS cells (LI90 and LX-2), the influences of HS cell CM (HS-CM) on proliferation and invasion of CC cells (HuCCT-1 and RBE), and the effects of their interaction on HUVEC tube formation were assessed using each CM. The effect of HS cells on tumor growth was examined in vivo by subcutaneous co-injection. Cytokine array was performed to assess the secreted proteins induced by their coculture.
RESULTS: CC-CM activated HS cells and increased their proliferation. HS-CM dose-dependently increased CC cell proliferation and invasion. Chemotherapy of CC cells was less effective when treated with HS-CM. HS-CM activated the mitogen-activated protein kinase and Akt pathways in tumor cells. The indirect interaction of CC and HS cells promotes tube formation of human umbilical venous endothelial cells. Subcutaneous co-injection of tumor cells with HS cells in nude mouse resulted in increased tumor size. Several proteins were found in the culture medium induced by their coculture, thought to be key proteins which regulated tumor-stromal interaction.
CONCLUSIONS: This study indicates that HS cells play an important role in accelerating cholangiocarcinoma progression and may be a therapeutic target in cholangiocarcinoma.
Hirohisa Okabe; Toru Beppu; Hiromitsu Hayashi; Takatoshi Ishiko; Toshiro Masuda; Ryu Otao; Hasita Horlad; Hirohumi Jono; Mitsuharu Ueda; Satoru Shinriki Phd; Yukio Ando; Hideo Baba
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Publication Detail:
Type:  Journal Article     Date:  2010-11-02
Journal Detail:
Title:  Annals of surgical oncology     Volume:  18     ISSN:  1534-4681     ISO Abbreviation:  Ann. Surg. Oncol.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9420840     Medline TA:  Ann Surg Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1175-84     Citation Subset:  IM    
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
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