| Cytoplasmic accumulation of connexin32 expands cancer stem cell population in human HuH7 hepatoma cells by enhancing its self-renewal. | |
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MedLine Citation:
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PMID: 20209499 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Yohei Kawasaki; Yasufumi Omori; Qingchang Li; Yuji Nishikawa; Toshiaki Yoshioka; Masayuki Yoshida; Kazuo Ishikawa; Katsuhiko Enomoto |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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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:
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Created Date: 2010-10-28 Completed Date: 2010-12-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 51-62 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 UICC. |
Affiliation:
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Department of Molecular and Tumour Pathology, Akita University Graduate School of Medicine, Akita, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals 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 Humans Immunoblotting Liver Neoplasms, Experimental / genetics, metabolism, pathology Male Mice Mice, SCID Neoplasm Metastasis Neoplastic Stem Cells / metabolism*, pathology Tetracycline / pharmacology Transplantation, Heterologous |
| Chemical | |
Reg. No./Substance:
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0/Anti-Bacterial Agents; 0/Connexins; 0/connexin 32; 564-25-0/Doxycycline; 60-54-8/Tetracycline |
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