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.
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 humancancer(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.
Authors: D Salonga; K D Danenberg; M Johnson; R Metzger; S Groshen; D D Tsao-Wei; H J Lenz; C G Leichman; L Leichman; R B Diasio; P V Danenberg Journal: Clin Cancer Res Date: 2000-04 Impact factor: 12.531
Authors: Lucia Kucerova; Miroslava Matuskova; Kristina Hlubinova; Roman Bohovic; Lucia Feketeova; Pavol Janega; Pavel Babal; Martina Poturnajova Journal: Cancer Lett Date: 2011-07-26 Impact factor: 8.679
Authors: Jian Wang; Per Ø Sakariassen; Oleg Tsinkalovsky; Heike Immervoll; Stig Ove Bøe; Agnete Svendsen; Lars Prestegarden; Gro Røsland; Frits Thorsen; Linda Stuhr; Anders Molven; Rolf Bjerkvig; Per Ø Enger Journal: Int J Cancer Date: 2008-02-15 Impact factor: 7.396