Thyroid cancer stem-like cells and epithelial-mesenchymal transition in thyroid cancers.

Cancer stem-like cells are a subpopulation of self-renewing stem cells in cancers that are more resistant to chemotherapy and radiation therapy. Evidence supporting the existence of cancer stem-like cells in thyroid and in many other solid tissue cancers is rapidly accumulating. These cells have been studied using specific biomarkers such as CD133, CD44, and aldehyde dehydrogenase enzymes. Putative cancer stem-like cells can be studied in vitro using serum-free media supplemented with basic fibroblast growth factor and epidermal growth factor grown in nonadherent culture (ultra-low attachment plates) or in extracellular matrix leading to cell spheres formation in vitro. Cancer stem-like cells can also be separated by fluorescent cell sorting and used for in vitro or in vivo studies. Injection of enriched populations of cancer stem-like cells (also referred to as tumor initiating cells) into immunodeficient mice often results in rapid growth of xenografts, which express cancer stem-like cell biomarkers. Human cancer stem-like cells have been identified in thyroid cancer cell lines including papillary, follicular, medullary, and anaplastic carcinoma cell lines. They have also been identified in primary thyroid cancers and have been shown to have similar properties as the cancer stem-like cells in thyroid cancer cell lines. Immunohistochemical staining with CD133 and other biomarkers has been used to characterize thyroid cancer stem-like cells in paraffin sections of thyroid cancers. Recent studies of epithelial-mesenchymal transition in which cells lose their epithelial features and acquire mesenchymal phenotypes have shown that these changes are present in thyroid cancers. Biomarkers used to characterize epithelial-mesenchymal transition have also been studied in primary thyroid cancers. A close relationship between epithelial-mesenchymal transition and stem cell features of cancers has been identified in recent studies. New discoveries in this field may lead to more effective therapies for highly aggressive and lethal thyroid cancers.