دورية أكاديمية
ABCG1 and Pgp identify drug resistant, self-renewing osteosarcoma cells.
| العنوان: | ABCG1 and Pgp identify drug resistant, self-renewing osteosarcoma cells. |
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| المؤلفون: | Roundhill EA; Children's Cancer Research Group, Leeds Institute of Cancer and Pathology, St. James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK. Electronic address: e.a.roundhill@leeds.ac.uk., Jabri S; Children's Cancer Research Group, Leeds Institute of Cancer and Pathology, St. James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK., Burchill SA; Children's Cancer Research Group, Leeds Institute of Cancer and Pathology, St. James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK. Electronic address: s.a.burchill@leeds.ac.uk. |
| المصدر: | Cancer letters [Cancer Lett] 2019 Jul 01; Vol. 453, pp. 142-157. Date of Electronic Publication: 2019 Mar 22. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Ireland Country of Publication: Ireland NLM ID: 7600053 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7980 (Electronic) Linking ISSN: 03043835 NLM ISO Abbreviation: Cancer Lett Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Limerick : Elsevier Science Ireland Original Publication: Amsterdam, Elsevier/North-Holland. |
| مواضيع طبية MeSH: | ATP Binding Cassette Transporter, Subfamily B, Member 1/*metabolism , ATP Binding Cassette Transporter, Subfamily G, Member 1/*metabolism , Antineoplastic Agents/*pharmacology , Bone Neoplasms/*drug therapy , Bone Neoplasms/*metabolism , Osteosarcoma/*drug therapy , Osteosarcoma/*metabolism, ATP Binding Cassette Transporter, Subfamily G, Member 1/biosynthesis ; ATP Binding Cassette Transporter, Subfamily G, Member 1/genetics ; Bone Neoplasms/genetics ; Bone Neoplasms/pathology ; Cell Growth Processes/drug effects ; Cell Line, Tumor ; Dactinomycin/pharmacology ; Doxorubicin/pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Etoposide/pharmacology ; HEK293 Cells ; Hep G2 Cells ; Humans ; MCF-7 Cells ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Osteosarcoma/genetics ; Osteosarcoma/pathology ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Vincristine/pharmacology |
| مستخلص: | 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. (Copyright © 2019 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: ABC transporter; Cancer stem-like cell; Chemotherapy; Osteosarcoma; Resistance |
| المشرفين على المادة: | 0 (ABCG1 protein, human) 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1) 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1) 0 (Antineoplastic Agents) 0 (RNA, Messenger) 1CC1JFE158 (Dactinomycin) 5J49Q6B70F (Vincristine) 6PLQ3CP4P3 (Etoposide) 80168379AG (Doxorubicin) |
| تواريخ الأحداث: | Date Created: 20190327 Date Completed: 20200325 Latest Revision: 20200325 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.canlet.2019.03.011 |
| PMID: | 30910588 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1872-7980 |
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| DOI: | 10.1016/j.canlet.2019.03.011 |