Roundhill, EA, Jabri, S and Burchill, SA (2019) ABCG1 and Pgp identify drug resistant, self-renewing osteosarcoma cells. Cancer Letters, 453. pp. 142-157. ISSN 0304-3835
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | Osteosarcoma; ABC transporter; Resistance; Cancer stem-like cell; Chemotherapy |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Experimental Oncology (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Section of Experimental Oncology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 09 May 2019 10:03 |
Last Modified: | 09 May 2019 10:03 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.canlet.2019.03.011 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:145807 |