Stemness in human thyroid cancers and derived cell lines: the role of asymmetrically dividing cancer stem cells resistant to chemotherapy.
BACKGROUND
Cancer stem cells (CSCs) have the ability to self-renew through symmetric and asymmetric cell division. CSCs may arise from mutations within an embryonic stem cell/progenitor cell population or via epithelial-mesenchymal transition (EMT), and recent advances in the study of thyroid stem cells have led to a growing recognition of the likely central importance of CSCs in thyroid tumorigenesis.


OBJECTIVE
The objectives of this study were to establish the presence of a stem cell population in human thyroid tumors and to identify, isolate, and characterize CSCs in thyroid cancer cell lines.


RESULTS
1) Human thyroid cancers (n = 10) and thyroid cancer cell lines (n = 6) contained a stem cell population as evidenced by pluripotent stem cell gene expression. 2) Pulse-chase experiments with thyroid cancer cells identified a label-retaining cell population, a primary characteristic of CSCs, which at mitosis divided their DNA both symmetrically and asymmetrically and included a population of cells expressing the progenitor marker, stage-specific embryonic antigen 1 (SSEA-1). 3) Cells positive for SSEA-1 expressed additional stem cell markers including Oct4, Sox2, and Nanog were confirmed as CSCs by their tumor-initiating properties in vivo, their resistance to chemotherapy, and their multipotent capability. 4) SSEA-1-positive cells showed enhanced vimentin expression and decreased E-cadherin expression, indicating their likely derivation via EMT.


CONCLUSIONS
Cellular diversity in thyroid cancer occurs through both symmetric and asymmetric cell division, and SSEA-1-positive cells are one form of CSCs that appear to have arisen via EMT and may be the source of malignant thyroid tumor formation. This would suggest that thyroid cancer CSCs were the result of thyroid cancer transformation rather than the source.
Thyroid Research Unit, Icahn School of Medicine at Mount Sinai, and the James J. Peters VA Medical Center, New York, New York 10468.
Risheng
R
Ma
Noga
N
Minsky
Syed A
SA
Morshed
Terry F
TF
Davies
D000818:Animals; D002291:Carcinoma, Papillary / Q000188:drug therapy / Q000473:pathology*; D002455:Cell Division; D016764:Cell Polarity; D002469:Cell Separation; D019008:Drug Resistance, Neoplasm; D006801:Humans; D016256:Lewis X Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D039904:Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D016256:Lewis X Antigen