In Vivo 5FU-Exposed Human Medullary Thyroid Carcinoma Cells Contain a Chemoresistant CD133+Tumor-Initiating Cell Subset

0429587 - ÚOCHB 2015 RIV US eng J - Článek v odborném periodiku
Kučerová, L. - Feketeová, L. - Kozovská, Z. - Poturnajová, M. - Matusková, M. - Nencka, Radim - Babál, P.
In Vivo 5FU-Exposed Human Medullary Thyroid Carcinoma Cells Contain a Chemoresistant CD133+Tumor-Initiating Cell Subset.
Thyroid. Roč. 24, č. 3 (2014), s. 520-532. ISSN 1050-7256. E-ISSN 1557-9077
Institucionální podpora: RVO:61388963
Klíčová slova: cancer stem cells * thymidylate synthase * colorectal cancer
Kód oboru RIV: FB - Endokrinologie, diabetologie, metabolizmus, výživa
Impakt faktor: 4.493, rok: 2014

Background: The hierarchical model of solid tumor proposes the existence of rare tumor cell subpopulations with stem-cell properties. The glycoprotein prominin-1 (CD133) represents one of the cancer stem-cell markers in several tumor types. The CD133+ cell subpopulation was shown to be enriched for tumor-initiating and highly chemoresistant cells in human cancer(s). Methods: We investigated whether CD133+ cells derived from human medullary thyroid carcinoma (MTC) possess tumor-initiating properties in vivo and exhibit differential responses to chemotherapeutic agents. We demonstrated that separated CD133+ cells from the human MTC cell line TT are enriched for tumor-initiating cells as demonstrated by tumor formation in vivo. Nevertheless, TT CD133+ cells do not exhibit increased chemoresistance in comparison to parental cells. However, when MTC xenotransplants were treated with the chemotherapeutic drug 5-fluorouracil (5FU) in vivo, CD133 expression increased in MTC cells. Results: This cell line, designated FTTiv isolated from the drug-exposed xenotransplants, exhibits a significantly different response to 5FU associated with the substantial change in the expression profile of genes involved in 5FU metabolism and drug resistance. Moreover, the CD133+ tumor-initiating subpopulation derived from these drug-exposed FTTiv cells is significantly more resistant to 5FU and retains the chemoresistant properties upon FTTiv culture propagation. Conclusions: These data suggest that the chemoresistant phenotype and the CD133+ MTC subpopulation emerged in response to chemotherapy in vivo.
Trvalý link: http://hdl.handle.net/11104/0234700