Cancer Stem Cells are Depolarized Relative to Normal Stem Cells Derived from Human Livers
Introduction and aim. The inability to distinguish cancer (CSCs) from normal stem cells (NSCs) has hindered attempts to identify safer, more effective therapies for hepatocellular carcinoma (HCC). The aim of this study was to document and compare cell membrane potential differences (PDs) of CSCs and...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-03-01
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| Series: | Annals of Hepatology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268119303953 |
| _version_ | 1818602782743068672 |
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| author | Wendy Bautista Jeremy Lipschitz Andrew McKay Gerald Y. Minuk |
| author_facet | Wendy Bautista Jeremy Lipschitz Andrew McKay Gerald Y. Minuk |
| author_sort | Wendy Bautista |
| collection | DOAJ |
| description | Introduction and aim. The inability to distinguish cancer (CSCs) from normal stem cells (NSCs) has hindered attempts to identify safer, more effective therapies for hepatocellular carcinoma (HCC). The aim of this study was to document and compare cell membrane potential differences (PDs) of CSCs and NSCs derived from human HCC and healthy livers respectively and determine whether altered GABAergic innervation could explain the differences.Material and methods. Epithelial cell adhesion molecule (EpCAM) positive stem cells were isolated from human liver tissues by magnetic bead separations. Cellular PDs were recorded by microelectrode impalement of freshly isolated cells. GABAA receptor subunit expression was documented by reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence.Results. CSCs were significantly depolarized (-7.0 ± 1.3 mV) relative to NSCs (-23.0 ± 1.4 mV, p < 0.01). The depolarized state was associated with different GABAA receptor subunit expression profiles wherein phasic transmission, represented by GAGAA a3 subunit expression, was prevalent in CSCs while tonic transmission, represented by GABAA a6 subunit expression, prevailed in NSCs. In addition, GABAA subunits a3, |33, y3 and S were strongly expressed in CSCs while GABAA n expression was dominant in NSCs. CSCs and NSCs responded similarly to GABAA receptor agonists (APD: 12.5 ± 1.2 mV and 11.0 ± 3.5 mV respectively).Conclusion. The results of this study indicate that CSCs are significantly depolarized relative to NSCs and these differences are associated with differences in GABAA receptor subunit expression. Together they provide new insights into the pathogenesis and possible treatment of human HCC. |
| first_indexed | 2024-12-16T13:12:45Z |
| format | Article |
| id | doaj.art-dcfd8d5f03d24612bea3a2fd73dac595 |
| institution | Directory Open Access Journal |
| issn | 1665-2681 |
| language | English |
| last_indexed | 2024-12-16T13:12:45Z |
| publishDate | 2017-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Annals of Hepatology |
| spelling | doaj.art-dcfd8d5f03d24612bea3a2fd73dac5952022-12-21T22:30:34ZengElsevierAnnals of Hepatology1665-26812017-03-01162297303Cancer Stem Cells are Depolarized Relative to Normal Stem Cells Derived from Human LiversWendy Bautista0Jeremy Lipschitz1Andrew McKay2Gerald Y. Minuk3Section of Hepatology, Department of Medicine, University of Manitoba, Winnipeg, Manitoba, CanadaDepartment of Surgery, University of Manitoba, Winnipeg, Manitoba, CanadaDepartment of Surgery, University of Manitoba, Winnipeg, Manitoba, CanadaCorrespondence and reprint request:; Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, CanadaIntroduction and aim. The inability to distinguish cancer (CSCs) from normal stem cells (NSCs) has hindered attempts to identify safer, more effective therapies for hepatocellular carcinoma (HCC). The aim of this study was to document and compare cell membrane potential differences (PDs) of CSCs and NSCs derived from human HCC and healthy livers respectively and determine whether altered GABAergic innervation could explain the differences.Material and methods. Epithelial cell adhesion molecule (EpCAM) positive stem cells were isolated from human liver tissues by magnetic bead separations. Cellular PDs were recorded by microelectrode impalement of freshly isolated cells. GABAA receptor subunit expression was documented by reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence.Results. CSCs were significantly depolarized (-7.0 ± 1.3 mV) relative to NSCs (-23.0 ± 1.4 mV, p < 0.01). The depolarized state was associated with different GABAA receptor subunit expression profiles wherein phasic transmission, represented by GAGAA a3 subunit expression, was prevalent in CSCs while tonic transmission, represented by GABAA a6 subunit expression, prevailed in NSCs. In addition, GABAA subunits a3, |33, y3 and S were strongly expressed in CSCs while GABAA n expression was dominant in NSCs. CSCs and NSCs responded similarly to GABAA receptor agonists (APD: 12.5 ± 1.2 mV and 11.0 ± 3.5 mV respectively).Conclusion. The results of this study indicate that CSCs are significantly depolarized relative to NSCs and these differences are associated with differences in GABAA receptor subunit expression. Together they provide new insights into the pathogenesis and possible treatment of human HCC.http://www.sciencedirect.com/science/article/pii/S1665268119303953Membrane potentialCancer stem cellNormal stem cellGABAHepatocellular carcinomaLiver |
| spellingShingle | Wendy Bautista Jeremy Lipschitz Andrew McKay Gerald Y. Minuk Cancer Stem Cells are Depolarized Relative to Normal Stem Cells Derived from Human Livers Annals of Hepatology Membrane potential Cancer stem cell Normal stem cell GABA Hepatocellular carcinoma Liver |
| title | Cancer Stem Cells are Depolarized Relative to Normal Stem Cells Derived from Human Livers |
| title_full | Cancer Stem Cells are Depolarized Relative to Normal Stem Cells Derived from Human Livers |
| title_fullStr | Cancer Stem Cells are Depolarized Relative to Normal Stem Cells Derived from Human Livers |
| title_full_unstemmed | Cancer Stem Cells are Depolarized Relative to Normal Stem Cells Derived from Human Livers |
| title_short | Cancer Stem Cells are Depolarized Relative to Normal Stem Cells Derived from Human Livers |
| title_sort | cancer stem cells are depolarized relative to normal stem cells derived from human livers |
| topic | Membrane potential Cancer stem cell Normal stem cell GABA Hepatocellular carcinoma Liver |
| url | http://www.sciencedirect.com/science/article/pii/S1665268119303953 |
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