Document Detail

Cytoplasmic accumulation of connexin32 expands cancer stem cell population in human HuH7 hepatoma cells by enhancing its self-renewal.
MedLine Citation:
PMID:  20209499     Owner:  NLM     Status:  MEDLINE    
Although the connexin32 (Cx32)-mediated gap junction is abolished in hepatocellular carcinoma (HCC), the expression of cytoplasmic Cx32 tends to increase in correspondence with the grade of malignancy. Establishing a Tet-off expression system in human nonmetastatic HuH7 HCC cells where cytoplasmic Cx32 was overexpressed by doxycycline (Dox) withdrawal, we previously demonstrated that overexpression of cytoplasmic Cx32 made HuH7 cells metastatic in mice. In our study, hypothesizing that the cytoplasmic Cx32-induced metastasis may involve expansion of the cancer stem cell (CSC) population, we examined whether cytoplasmic Cx32 controlled the size of the side population (SP) in HuH7 Tet-off Cx32 cells. Fluorescence-activated cell sorting revealed that SP was expanded in a Dox-free medium compared with a Dox-supplemented one. Although cytoplasmic Cx32 did not block maturation from SP to non-SP, purified SP reconstituted a larger SP fraction in the Dox-free medium than in the Dox-supplemented one. Furthermore, although SP from HuH7 Tet-off mock cells formed a similar number of CSC spheres of a similar size whether with or without Dox, SP from HuH7 Tet-off Cx32 cells developed a greater number of larger CSC spheres in the Dox-free medium than in the Dox-supplemented one. Taken together, these results suggest that accumulation of cytoplasmic Cx32 should enhance self-renewal of CSC to expand the CSC population in HCC.
Yohei Kawasaki; Yasufumi Omori; Qingchang Li; Yuji Nishikawa; Toshiaki Yoshioka; Masayuki Yoshida; Kazuo Ishikawa; Katsuhiko Enomoto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  128     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-10-28     Completed Date:  2010-12-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  51-62     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 UICC.
Department of Molecular and Tumour Pathology, Akita University Graduate School of Medicine, Akita, Japan.
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MeSH Terms
Anti-Bacterial Agents / pharmacology
Carcinoma, Hepatocellular / genetics,  metabolism*,  pathology
Cell Line, Tumor
Cell Proliferation*
Connexins / genetics,  metabolism*
Cytoplasm / drug effects,  metabolism
Doxycycline / pharmacology
Flow Cytometry
Fluorescent Antibody Technique, Indirect
Gene Expression / drug effects
Liver Neoplasms, Experimental / genetics,  metabolism,  pathology
Mice, SCID
Neoplasm Metastasis
Neoplastic Stem Cells / metabolism*,  pathology
Tetracycline / pharmacology
Transplantation, Heterologous
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Connexins; 0/connexin 32; 564-25-0/Doxycycline; 60-54-8/Tetracycline

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