Abstract
Patients with osteosarcoma (OST) frequently relapse with drug resistant disease, consistent with the hypothesis that tumours contain a cancer stem-like cell (CSCs) population that survives chemotherapy to re-populate the tumour at local or metastatic sites. We describe a dual functional approach to isolate OST-CSCs and identify the ABC transporter proteins driving this population to reveal potential targets for the development of new treatments. OST-CSCs were isolated by selection in doxorubicin (OST-EC50 cells) and based on the ability to produce progeny from a single cell (HOS-EC50.SR cells). Pgp expression was increased in OST-EC50 cells, inducing resistance to doxorubicin, etoposide, vincristine and actinomycin D (p < 0.05). Increased expression of ABCG1 and Pgp protein in the HOS-EC50.SR cells induced resistance to etoposide and doxorubicin (p < 0.01), which was directly correlated with ABCG1 expression (r > 0.88, p < 0.001). Pgp expression is increased in both the HOS-EC50 cells where it mediates MDR and the HOS-EC50.SR populations, whereas ABCG1 was only upregulated in the self-renewing drug resistant HOS-EC50.SR cells. Targeting ABCG1 and Pgp may eradicate the drug resistant self-renewing OST-CSCs, leading to improved outcomes for patients with OST.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
