Abstract
Emerging evidence suggests cancer stem cells (CSCs) may initiate new tumors in anaplastic thyroid carcinoma (ATC), one of the most aggressive solid tumors in humans. However, the involvement of CSCs in human tumorigenesis has not been previously studied in authenticated ATC cell lines. Here we demonstrate a functional role of CSCs in four new validated human ATC cell lines (THJ-11T, THJ-16T, THJ-21T and THJ-29T). We identified and enriched CSCs using a spheroid-forming assay. About 3 to 9% of cells from four ATC cell lines formed thyrospheres. The thyrospheres expressed the stem cell markers NANOG and Oct4 and possessed the ability to self-renew. Injection of these thyrospheres into the thyroids of NOD/SCID Il2rg-/- mice resulted in the formation of metastatic tumors that recapitulated the clinical features of human ATC. To our knowledge, this is the first in vivo characterization of thyroid CSCs using validated human ATC cell lines. The availability of disease-specific thyrospheres and our orthotopic tumor models will enable the elucidation of disease mechanisms and the environmental niche of CSCs. They may also be useful for preclinical therapeutic screening and for monitoring the effects of biological therapies on ATC.
Highlights
Anaplastic thyroid carcinoma (ATC) is one of the most lethal human malignancies
ATC cells maintain clonogenic capacity in vitro We first studied the proliferation of four human ATC cell lines: THJ-11T (p67), THJ-16T (p88), THJ-21T (p56) and THJ-29T (p89)
Real-time quantitative reverse transcriptase-PCR analysis showed that all cell lines expressed paired box gene 8 (Pax8), a thyroid-specific transcription factor
Summary
Anaplastic thyroid carcinoma (ATC) is one of the most lethal human malignancies. Ninety percent of patients with ATC die within six months of diagnosis. It is relatively rare — it accounts for only 2% of all thyroid cancer cases — ATC causes more than 50% of all thyroid cancer deaths every year. Current treatments for ATC are aggressive, and include surgery, chemotherapy and radiation therapy. ATC is resistant to all types of therapy and disease prognosis has remained unchanged for more than 50 years [1]. ATC is a major diagnostic and therapeutic challenge
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