CD133-expressing thyroid cancer cells are undifferentiated, radioresistant and survive radioiodide therapy.
OBJECTIVE
(131)I 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 (131)I 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.


CONCLUSIONS
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.
Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan.
Chien-Chih
CC
Ke
Ren-Shyan
RS
Liu
An-Hang
AH
Yang
Ching-Sheng
CS
Liu
Chin-Wen
CW
Chi
Ling-Ming
LM
Tseng
Yi-Fan
YF
Tsai
Jennifer H
JH
Ho
Chen-Hsen
CH
Lee
Oscar K
OK
Lee
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000528:radiation effects; D002454:Cell Differentiation / Q000528:radiation effects; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000528:radiation effects*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011836:Radiation Tolerance; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D014183:Transplantation, Heterologous
D000071916:AC133 Antigen; D015703:Antigens, CD; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D007457:Iodine Radioisotopes; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse