Characterisation of mesothelioma-initiating cells and their susceptibility to anti-cancer agents.

Abstract

Malignant mesothelioma (MM) is an aggressive type of tumour causing high mortality. One reason for this paradigm may be the existence of a subpopulation of tumour-initiating cells (TICs) that endow MM with drug resistance and recurrence. The objective of this study was to identify and characterise a TIC subpopulation in MM cells, using spheroid cultures, mesospheres, as a model of MM TICs. Mesospheres, typified by the stemness markers CD24, ABCG2 and OCT4, initiated tumours in immunodeficient mice more efficiently than adherent cells. CD24 knock-down cells lost the sphere-forming capacity and featured lower tumorigenicity. Upon serial transplantation, mesospheres were gradually more efficiently tumrigenic with increased level of stem cell markers. We also show that mesospheres feature mitochondrial and metabolic properties similar to those of normal and cancer stem cells. Finally, we show that mesothelioma-initiating cells are highly susceptible to mitochondrially targeted vitamin E succinate. This study documents that mesospheres can be used as a plausible model of mesothelioma-initiating cells and that they can be utilised in the search for efficient agents against MM.

• Authors: Elham Alizadeh Pasdar, Michael Smits, Michael Stapelberg, Martina Bajzikova, Marina Stantic, Jacob Goodwin, Bing Yan, Jan Stursa, Jaromira Kovarova, Karishma Sachaphibulkij, Ayenachew Bezawork-Geleta, Margaryta Sobol, Anatoly Filimonenko, Marco Tomasetti, Renata Zobalova, Pavel Hozak, Lan-Feng Dong, Jiri Neuzil
• Journal: PloS one (PLoS One) Vol. 10 Issue 5 Pg. e0119549 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25932953 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• CD24 Antigen
• Tocopherols

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Biomarkers, Tumor (metabolism)
• CD24 Antigen (metabolism)
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Disease Progression
• Gene Knockdown Techniques
• Humans
• Inhibitory Concentration 50
• Lung Neoplasms (metabolism, pathology)
• Mesothelioma (metabolism, pathology)
• Mesothelioma, Malignant
• Mice, Nude
• Mitochondria (drug effects, metabolism)
• Neoplasm Invasiveness
• Neoplasm Transplantation
• Neoplastic Stem Cells (drug effects, metabolism, pathology)
• Phenotype
• Spheroids, Cellular (drug effects, pathology)
• Tocopherols (pharmacology)