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BMC Cancer. 2012; 12: 139.
Published online Apr 4, 2012. doi:  10.1186/1471-2407-12-139
PMCID: PMC3351999
Therapeutic implications of an enriched cancer stem-like cell population in a human osteosarcoma cell line
Sara R Martins-Neves,1 Áurio O Lopes,1 Anália do Carmo,2,3 Artur A Paiva,4 Paulo C Simões,5 Antero J Abrunhosa,3,6 and Célia MF Gomescorresponding author1,3
1Pharmacology and Experimental Therapeutics - Institute of Biomedical Research in Light and Image (IBILI), Faculty of Medicine, University of Coimbra, Az. de Sta. Comba, Celas, Coimbra 3000-354, Portugal
2Center for Neurosciences and Cell Biology (CNC), Coimbra, Portugal
3Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal
4Histocompatibility Centre, University Hospital of Coimbra, Coimbra, Portugal
5Radiotherapy Service, University Hospital of Coimbra, Coimbra, Portugal
6Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, Coimbra, Portugal
corresponding authorCorresponding author.
Sara R Martins-Neves: sara.neves87/at/gmail.com; Áurio O Lopes: olopes10/at/hotmail.com; Anália do Carmo: analiacarmo/at/gmail.com; Artur A Paiva: apaiva/at/histocentro.min-saude.pt; Paulo C Simões: cesar/at/huc.min-saude.pt; Antero J Abrunhosa: antero/at/pet.uc.pt; Célia MF Gomes: cgomes/at/ibili.uc.pt
Received December 16, 2011; Accepted April 4, 2012.
Abstract
Background
Osteosarcoma is a bone-forming tumor of mesenchymal origin that presents a clinical pattern that is consistent with the cancer stem cell model. Cells with stem-like properties (CSCs) have been identified in several tumors and hypothesized as the responsible for the relative resistance to therapy and tumor relapses. In this study, we aimed to identify and characterize CSCs populations in a human osteosarcoma cell line and to explore their role in the responsiveness to conventional therapies.
Methods
CSCs were isolated from the human MNNG/HOS cell line using the sphere formation assay and characterized in terms of self-renewal, mesenchymal stem cell properties, expression of pluripotency markers and ABC transporters, metabolic activity and tumorigenicity. Cell's sensitivity to conventional chemotherapeutic agents and to irradiation was analyzed and related with cell cycle-induced alterations and apoptosis.
Results
The isolated CSCs were found to possess self-renewal and multipotential differentiation capabilities, express markers of pluripotent embryonic stem cells Oct4 and Nanog and the ABC transporters P-glycoprotein and BCRP, exhibit low metabolic activity and induce tumors in athymic mice. Compared with parental MNNG/HOS cells, CSCs were relatively more resistant to both chemotherapy and irradiation. None of the treatments have induced significant cell-cycle alterations and apoptosis in CSCs.
Conclusions
MNNG/HOS osteosarcoma cells contain a stem-like cell population relatively resistant to conventional chemotherapeutic agents and irradiation. This resistant phenotype appears to be related with some stem features, namely the high expression of the drug efflux transporters P-glycoprotein and BCRP and their quiescent nature, which may provide a biological basis for resistance to therapy and recurrence commonly observed in osteosarcoma.
Keywords: Osteosarcoma, Cancer stem-like cells, Resistance, Chemotherapy, Radiotherapy
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