[RETRACTED] Platelet-derived growth factor receptor-α and -β promote cancer stem cell phenotypes in sarcomas Journal Article
| Authors: | Chang, K. K.; Yoon, C.; Yi, B. C.; Tap, W. D.; Simon, M. C.; Yoon, S. S. |
| Article Title: | [RETRACTED] Platelet-derived growth factor receptor-α and -β promote cancer stem cell phenotypes in sarcomas |
| Abstract: | Sarcomas are malignant tumors derived from mesenchymal tissues and may harbor a subset of cells with cancer stem-like cell (CSC) properties. Platelet-derived growth factor receptors α and β (PDGFR-α/β) play an important role in the maintenance of mesenchymal stem cells. Here we examine the role of PDGFR-α/β in sarcoma CSCs. PDGFR-α/β activity and the effects of PDGFR-α/β inhibition were examined in 3 human sarcoma cell lines using in vitro assays and mouse xenograft models. In all three cell lines, PDGFR-α/β activity was significantly higher in cells grown as spheroids (to enrich for CSCs) and in cells sorted for CD133 expression (a marker of sarcoma CSCs). Self-renewal transcription factors Nanog, Oct4, and Slug and epithelial-to-mesenchymal transition (EMT) proteins Snail, Slug, and Zeb1 were also significantly higher in spheroids cells and CD133(+) cells. Spheroid cells and CD133(+) cells demonstrated 2.9- to 4.2-fold greater migration and invasion and resistance to doxorubicin chemotherapy. Inhibition of PDGFR-α/β in CSCs using shRNA or pharmacologic inhibitors reduced expression of certain self-renewal and EMT proteins, reduced spheroid formation by 74-82%, reduced migration and invasion by 73-80%, and reversed chemotherapy resistance. In mouse xenograft models, combining PDGFR-α/β inhibition (using shRNA or imatinib) with doxorubicin had a more-than-additive effect in blocking tumor growth, with enhanced apoptosis, especially in CD133(+) cells. These results indicate that PDGFR-α/β activity is upregulated in sarcoma CSCs and promote CSC phenotypes including migration, invasion, and chemotherapy resistance. Thus, the PDGFR-α/β pathway represents a new potential therapeutic target to reduce metastatic potential and increase chemosensitivity. © 2018 The Author(s). |
| Journal Title: | Oncogenesis |
| Volume: | 7 |
| Issue: | 6 |
| ISSN: | 2157-9024 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2018-06-19 |
| Start Page: | 47 |
| Language: | English |
| DOI: | 10.1038/s41389-018-0059-1 |
| PROVIDER: | scopus |
| PMCID: | PMC6006341 |
| PUBMED: | 29915281 |
| DOI/URL: | |
| Notes: | Retraction issued, see DOI: 10.1038/s41389-024-00520-7 -- Source: Scopus |
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