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Selective Calcium S...
Selective Calcium Sensitivity in Immature Glioma Cancer Stem Cells
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Wee, Shimei (författare)
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- Niklasson, Maria (författare)
- Department of Medical Biochemistry and Biophysics, Karolinska Institutet
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- Marinescu, Voichita Dana (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Segerman, Anna (författare)
- Uppsala universitet,Neuroonkologi
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- Schmidt, Linnea (författare)
- Uppsala universitet,Neuroonkologi
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- Hermansson, Annika (författare)
- Uppsala universitet,Neuroonkologi
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Dirks, Peter (författare)
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- Forsberg-Nilsson, Karin (författare)
- Uppsala universitet,Neuroonkologi
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- Westermark, Bengt (författare)
- Uppsala universitet,Neuroonkologi
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- Uhrbom, Lene (författare)
- Uppsala universitet,Neuroonkologi
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- Linnarsson, Sten (författare)
- Karolinska Institutet
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- Nelander, Sven (författare)
- Uppsala universitet,Neuroonkologi
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- Andang, Michael (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2014-12-22
- 2014
- Engelska.
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12
- Relaterad länk:
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https://uu.diva-port... (primary) (Raw object)
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https://journals.plo...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Tumor-initiating cells are a subpopulation in aggressive cancers that exhibit traits shared with stem cells, including the ability to self-renew and differentiate, commonly referred to as stemness. In addition, such cells are resistant to chemo- and radiation therapy posing a therapeutic challenge. To uncover stemness-associated functions in glioma-initiating cells (GICs), transcriptome profiles were compared to neural stem cells (NSCs) and gene ontology analysis identified an enrichment of Ca2+ signaling genes in NSCs and the more stem-like (NSC-proximal) GICs. Functional analysis in a set of different GIC lines regarding sensitivity to disturbed homeostasis using A23187 and Thapsigargin, revealed that NSC-proximal GICs were more sensitive, corroborating the transcriptome data. Furthermore, Ca2+ drug sensitivity was reduced in GICs after differentiation, with most potent effect in the NSC-proximal GIC, supporting a stemness-associated Ca2+ sensitivity. NSCs and the NSC-proximal GIC line expressed a larger number of ion channels permeable to potassium, sodium and Ca2+. Conversely, a higher number of and higher expression levels of Ca2+ binding genes that may buffer Ca2+, were expressed in NSC-distal GICs. In particular, expression of the AMPA glutamate receptor subunit GRIA1, was found to associate with Ca2+ sensitive NSC-proximal GICs, and decreased as GICs differentiated along with reduced Ca2+ drug sensitivity. The correlation between high expression of Ca2+ channels (such as GRIA1) and sensitivity to Ca2+ drugs was confirmed in an additional nine novel GIC lines. Calcium drug sensitivity also correlated with expression of the NSC markers nestin (NES) and FABP7 (BLBP, brain lipid-binding protein) in this extended analysis. In summary, NSC-associated NES+/FABP7(+)/GRIA1(+) GICs were selectively sensitive to disturbances in Ca2+ homeostasis, providing a potential target mechanism for eradication of an immature population of malignant cells.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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PLOS ONE
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Wee, Shimei
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Niklasson, Maria
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Marinescu, Voich ...
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Segerman, Anna
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Schmidt, Linnea
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Hermansson, Anni ...
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Dirks, Peter
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Forsberg-Nilsson ...
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Westermark, Beng ...
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Uhrbom, Lene
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Linnarsson, Sten
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Nelander, Sven
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Andang, Michael
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