ABCG1 and Pgp identify drug resistant, self-renewing osteosarcoma cells
| Autor: | Susan A. Burchill, Elizabeth Ann Roundhill, Sara Jabri |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Vincristine medicine.medical_treatment Population Antineoplastic Agents Bone Neoplasms Cell Growth Processes Drug resistance Biology 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Humans Doxorubicin ATP Binding Cassette Transporter Subfamily B Member 1 RNA Messenger education Etoposide ATP Binding Cassette Transporter Subfamily G Member 1 Osteosarcoma Chemotherapy education.field_of_study fungi Cancer Hep G2 Cells medicine.disease Drug Resistance Multiple HEK293 Cells 030104 developmental biology Oncology Drug Resistance Neoplasm 030220 oncology & carcinogenesis Dactinomycin MCF-7 Cells Neoplastic Stem Cells Cancer research medicine.drug |
| Zdroj: | Cancer Letters. 453:142-157 |
| ISSN: | 0304-3835 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect