CD133-expressing thyroid cancer cells are undifferentiated, radioresistant and survive radioiodide therapy
131I therapy is regularly used following surgery as a part of thyroid cancer management. Despite an overall relatively good prognosis, recurrent or metastatic thyroid cancer is not rare. CD133-expressing cells have been shown to mark thyroid cancer stem cells that possess the characteristics of stem cells and have the ability to initiate tumours. However, no studies have addressed the influence of CD133-expressing cells on radioiodide therapy of the thyroid cancer. The aim of this study was to investigate whether CD133+ cells contribute to the radioresistance of thyroid cancer and thus potentiate future recurrence and metastasis.
Thyroid cancer cell lines were analysed for CD133 expression, radiosensitivity and gene expression.
The anaplastic thyroid cancer cell line ARO showed a higher percentage of CD133+ cells and higher radioresistance. After γ-irradiation of the cells, the CD133+ population was enriched due to the higher apoptotic rate of CD133− cells. In vivo 131I treatment of ARO tumour resulted in an elevated expression of CD133, Oct4, Nanog, Lin28 and Glut1 genes. After isolation, CD133+ cells exhibited higher radioresistance and higher expression of Oct4, Nanog, Sox2, Lin28 and Glut1 in the cell line or primarily cultured papillary thyroid cancer cells, and lower expression of various thyroid-specific genes, namely NIS, Tg, TPO, TSHR, TTF1 and Pax8.
This study demonstrates the existence of CD133-expressing thyroid cancer cells which show a higher radioresistance and are in an undifferentiated status. These cells possess a greater potential to survive radiotherapy and may contribute to the recurrence of thyroid cancer. A future therapeutic approach for radioresistant thyroid cancer may focus on the selective eradication of CD133+ cells.
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- CD133-expressing thyroid cancer cells are undifferentiated, radioresistant and survive radioiodide therapy
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European Journal of Nuclear Medicine and Molecular Imaging
Volume 40, Issue 1 , pp 61-71
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- Thyroid cancer
- Cancer stem cell
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- Author Affiliations
- 1. Institute of Clinical Medicine, National Yang Ming University, Taipei, 11221, Taiwan
- 2. Molecular and Genetic Imaging Core, NRPGM, Taipei, 11221, Taiwan
- 3. School of Medicine, National Yang-Ming University, Taipei, 11221, Taiwan
- 4. National PET/Cyclotron Center, Taipei Veterans General Hospital, Taipei, 11221, Taiwan
- 5. Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 11221, Taiwan
- 6. Department of Nuclear Medicine, School of Medicine, National Yang-Ming University Medical School, Taipei, 11221, Taiwan
- 8. Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, 11221, Taiwan
- 9. Department of Pathology, School of Medicine, National Yang-Ming University, Taipei, 11221, Taiwan
- 10. Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, 11221, Taiwan
- 16. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, 11221, Taiwan
- 7. Department of Surgery, Taipei Veterans General Hospital, Taipei, 11221, Taiwan
- 11. Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, 11031, Taiwan
- 12. Department of Ophthalmology, Taipei Medical University-Wan Fang Medical Center, Taipei, 11696, Taiwan
- 13. Center for Stem Cell Research, Taipei Medical University-Wan Fang Medical Center, Taipei, 11696, Taiwan
- 14. Department of Orthopedics, Taipei Veterans General Hospital, Taipei, 11221, Taiwan
- 15. Stem Cell Research Center, National Yang-Ming University, Taipei, 11221, Taiwan