Selective calcium sensitivity in immature glioma cancer stem cells

Shimei Wee, Maria Niklasson, Voichita Dana Marinescu, Anna Segerman, Linnéa Schmidt, Annika Hermansson, Peter Dirks, Karin Forsberg-Nilsson, Bengt Westermark, Lene Uhrbom, Sten Linnarsson, Sven Nelander, Michael Andäng, Alfredo Quinones-Hinojosa

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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 chemoand radiation therapy posing a therapeutic challenge. To uncover stemnessassociated 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 (NSCproximal) 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.

Original languageEnglish (US)
Article numbere115698
JournalPLoS One
Volume9
Issue number12
DOIs
StatePublished - Dec 22 2014
Externally publishedYes

Fingerprint

Neoplastic Stem Cells
Stem cells
Neural Stem Cells
Glioma
stem cells
immatures
Calcium
calcium
cells
Cells
Nestin
drugs
Genes
cell lines
Pharmaceutical Preparations
Transcriptome
transcriptome
Cell Line
neoplasm cells
homeostasis

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Wee, S., Niklasson, M., Marinescu, V. D., Segerman, A., Schmidt, L., Hermansson, A., ... Quinones-Hinojosa, A. (2014). Selective calcium sensitivity in immature glioma cancer stem cells. PLoS One, 9(12), [e115698]. https://doi.org/10.1371/journal.pone.0115698

Selective calcium sensitivity in immature glioma cancer stem cells. / Wee, Shimei; Niklasson, Maria; Marinescu, Voichita Dana; Segerman, Anna; Schmidt, Linnéa; Hermansson, Annika; Dirks, Peter; Forsberg-Nilsson, Karin; Westermark, Bengt; Uhrbom, Lene; Linnarsson, Sten; Nelander, Sven; Andäng, Michael; Quinones-Hinojosa, Alfredo.

In: PLoS One, Vol. 9, No. 12, e115698, 22.12.2014.

Research output: Contribution to journalArticle

Wee, S, Niklasson, M, Marinescu, VD, Segerman, A, Schmidt, L, Hermansson, A, Dirks, P, Forsberg-Nilsson, K, Westermark, B, Uhrbom, L, Linnarsson, S, Nelander, S, Andäng, M & Quinones-Hinojosa, A 2014, 'Selective calcium sensitivity in immature glioma cancer stem cells', PLoS One, vol. 9, no. 12, e115698. https://doi.org/10.1371/journal.pone.0115698
Wee S, Niklasson M, Marinescu VD, Segerman A, Schmidt L, Hermansson A et al. Selective calcium sensitivity in immature glioma cancer stem cells. PLoS One. 2014 Dec 22;9(12). e115698. https://doi.org/10.1371/journal.pone.0115698
Wee, Shimei ; Niklasson, Maria ; Marinescu, Voichita Dana ; Segerman, Anna ; Schmidt, Linnéa ; Hermansson, Annika ; Dirks, Peter ; Forsberg-Nilsson, Karin ; Westermark, Bengt ; Uhrbom, Lene ; Linnarsson, Sten ; Nelander, Sven ; Andäng, Michael ; Quinones-Hinojosa, Alfredo. / Selective calcium sensitivity in immature glioma cancer stem cells. In: PLoS One. 2014 ; Vol. 9, No. 12.
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