Original Article

European Journal of Nuclear Medicine and Molecular Imaging

, Volume 40, Issue 1, pp 61-71

Open Access This content is freely available online to anyone, anywhere at any time.

CD133-expressing thyroid cancer cells are undifferentiated, radioresistant and survive radioiodide therapy

  • Chien-Chih KeAffiliated withInstitute of Clinical Medicine, National Yang Ming University
  • , Ren-Shyan LiuAffiliated withInstitute of Clinical Medicine, National Yang Ming UniversityMolecular and Genetic Imaging Core, NRPGMSchool of Medicine, National Yang-Ming UniversityNational PET/Cyclotron Center, Taipei Veterans General HospitalDepartment of Biomedical Imaging and Radiological Sciences, National Yang-Ming UniversityDepartment of Nuclear Medicine, School of Medicine, National Yang-Ming University Medical School Email author 
  • , An-Hang YangAffiliated withDepartment of Pathology and Laboratory Medicine, Taipei Veterans General HospitalDepartment of Pathology, School of Medicine, National Yang-Ming University
  • , Ching-Sheng LiuAffiliated withDepartment of Nuclear Medicine, School of Medicine, National Yang-Ming University Medical School
  • , Chin-Wen ChiAffiliated withInstitute of Clinical Medicine, National Yang Ming UniversityInstitute of Pharmacology, School of Medicine, National Yang-Ming UniversityDepartment of Medical Research and Education, Taipei Veterans General Hospital
  • , Ling-Ming TsengAffiliated withInstitute of Clinical Medicine, National Yang Ming UniversityDepartment of Surgery, Taipei Veterans General Hospital
  • , Yi-Fan TsaiAffiliated withDepartment of Surgery, Taipei Veterans General Hospital
  • , Jennifer H. HoAffiliated withInstitute of Clinical Medicine, National Yang Ming UniversityGraduate Institute of Clinical Medicine, Taipei Medical UniversityDepartment of Ophthalmology, Taipei Medical University-Wan Fang Medical CenterCenter for Stem Cell Research, Taipei Medical University-Wan Fang Medical Center
  • , Chen-Hsen LeeAffiliated withMolecular and Genetic Imaging Core, NRPGMSchool of Medicine, National Yang-Ming UniversityDepartment of Surgery, Taipei Veterans General Hospital
    • , Oscar K. LeeAffiliated withInstitute of Clinical Medicine, National Yang Ming UniversityDepartment of Orthopedics, Taipei Veterans General HospitalStem Cell Research Center, National Yang-Ming UniversityDepartment of Medical Research and Education, Taipei Veterans General Hospital Email author 

Abstract

Purpose

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.

Methods

Thyroid cancer cell lines were analysed for CD133 expression, radiosensitivity and gene expression.

Results

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.

Conclusion

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.

Keywords

Thyroid cancer CD133 Cancer stem cell Radiotherapy 131I