Generation of Novel Thyroid Cancer Stem-Like Cell Clones
| Autor: | Jidong Chen, Herbert Chen, Ricardo V. Lloyd, Ranran Zhang, Carolina Larrain, Xiao-Min Yu, Heather Hardin, April D. Harrison |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty endocrine system diseases medicine.medical_treatment Thyroid Cancer Biology medicine.disease Stem cell marker Pathology and Forensic Medicine Metastasis Thyroid carcinoma Radiation therapy 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research medicine Anaplastic thyroid cancer Thyroid cancer |
| Zdroj: | The American Journal of Pathology. 186:1662-1673 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2016.02.003 |
| Popis: | Anaplastic thyroid cancer is an aggressive and highly lethal cancer for which conventional therapies have proved ineffective. Cancer stem-like cells (CSCs) represent a small fraction of cells in the cancer that are resistant to chemotherapy and radiation therapy and are responsible for tumor reoccurrence and metastasis. We characterized CSCs in thyroid carcinomas and generated clones of CSC lines. Our study showed that anaplastic thyroid cancers had significantly more CSCs than well-differentiated thyroid cancers. We also showed that Aldefluor-positive cells revealed significantly higher expression of stem cell markers, self-renewal properties, thyrosphere formation, and enhanced tumorigenicity. In vivo passaging of Aldefluor-positive cells resulted in the growth of larger, more aggressive tumors. We isolated and generated two clonal spheroid CSC lines derived from anaplastic thyroid cancer that were even more enriched with stem cell markers and more tumorigenic than the freshly isolated Aldefluor-positive cells. Resveratrol and valproic acid treatment of one of the CSC lines resulted in a significant decrease in stem cell markers, Aldefluor expression, proliferation, and invasiveness, with an increase in apoptosis and thyroid differentiation markers, suggesting that these cell lines may be useful for discovering new adjuvant therapies for aggressive thyroid cancers. For the first time, we have two thyroid CSC lines that will be useful tools for the study of thyroid CSC targeted therapies. |
| Databáze: | OpenAIRE |
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