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Cancer Cell International
Published in: Cancer Cell International 1/2017

Open Access 01-12-2017 | Research

Pleomorphism and drug resistant cancer stem cells are characteristic of aggressive primary meningioma cell lines

Authors: Ishaq Khan, Saleh Baeesa, Mohammed Bangash, Hans-Juergen Schulten, Fahad Alghamdi, Hanadi Qashqari, Nawal Madkhali, Angel Carracedo, Mohamad Saka, Awatif Jamal, Jaudah Al-Maghrabi, Mohammed AlQahtani, Saleh Al-Karim, Ghazi Damanhouri, Kulvinder Saini, Adeel Chaudhary, Adel Abuzenadah, Deema Hussein

Published in: Cancer Cell International | Issue 1/2017

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Abstract

Background

Meningioma tumors arise in arachnoid membranes, and are the most reported central nervous system (CNS) tumors worldwide. Up to 20% of grade I meningioma tumors reoccur and currently predictive cancer stem cells (CSCs) markers for aggressive and drug resistant meningiomas are scarce.

Methods

Meningioma tissues and primary cell lines were investigated using whole transcriptome microarray analysis, immunofluorescence staining of CSCs markers (including CD133, Sox2, Nestin, and Frizzled 9), and drug treatment with cisplatin or etoposide.

Results

Unsupervised hierarchical clustering of six meningioma samples separated tissues into two groups. Analysis identified stem cells related pathways to be differential between the two groups and indicated the de-regulation of the stem cell associated genes Reelin (RELN), Calbindin 1 (CALB1) and Anterior Gradient 2 Homolog (AGR2). Immunofluorescence staining for four tissues confirmed stemness variation in situ. Biological characterization of fifteen meningioma primary cell lines concordantly separated cells into two functionally distinct sub-groups. Pleomorphic cell lines (NG type) grew significantly faster than monomorphic cell lines (G type), had a higher number of cells that express Ki67, and were able to migrate aggressively in vitro. In addition, NG type cell lines had a lower expression of nuclear Caspase-3, and had a significantly higher number of CSCs co-positive for CD133+ Sox2+ or AGR2+ BMI1+. Importantly, these cells were more tolerant to cisplatin and etoposide treatment, showed a lower level of nuclear Caspase-3 in treated cells and harbored drug resistant CSCs.

Conclusion

Collectively, analyses of tissues and primary cell lines revealed stem cell associated genes as potential targets for aggressive and drug resistant meningiomas.
Appendix
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Metadata
Title
Pleomorphism and drug resistant cancer stem cells are characteristic of aggressive primary meningioma cell lines
Authors
Ishaq Khan
Saleh Baeesa
Mohammed Bangash
Hans-Juergen Schulten
Fahad Alghamdi
Hanadi Qashqari
Nawal Madkhali
Angel Carracedo
Mohamad Saka
Awatif Jamal
Jaudah Al-Maghrabi
Mohammed AlQahtani
Saleh Al-Karim
Ghazi Damanhouri
Kulvinder Saini
Adeel Chaudhary
Adel Abuzenadah
Deema Hussein
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2017
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-017-0441-7

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