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C-Terminal-PEDF Reduces IC50 Doses and Chemoresistant Population of CD133 and BCRP1-Positve Cancer Stem Like Cells
Pages 195-208
Paola Castro-Garcia, Carmen Gil-Gas, Paloma Honrubia-Gómez, Carmen Belen Alvarez-Simón, Jesús-José Ferré-Fernández, Francisco Sánchez-Sánchez, Jose Luis Sánchez-Sánchez, Jose Mª Garcia-Bueno, Sebastiá Sabater, Guadalupe Aparicio, Luis Miguel Antón-Aparicio and Carmen Ramírez-Castillejo
DOI: http://dx.doi.org/10.6000/1927-7229.2013.02.04.2

Published: 31 October 2013


Abstract: The cancer stem cell hypothesis suggests that cancer contains cancer cells with stemness characteristics, and also in immortalised cancer cell lines. This work analyzes the characteristics of the “cancer stem cell” population in C6 tumour cell line. We found a small population defined by the expression of two biomarkers, previously reported in both stem and cancer stem cells, with an aggressive phenotype injected in nude mice. We found 0.6% BCRP1+ cells, the principal protein responsible for the Side Population (SP). On the other hand, we found a small CD133+ positive population, a self-renewal related protein. Moreover, the entire CD133+ population matched with part of BCRP1+ cells suggesting that CD133+ cells could be a subpopulation of BCRP1+ cells, and therefore, a more specific cancer stem cell population than previously described for glioma C6 cell line. These CD133+/BCRP1+ cells display an aggressive phenotype when injected into NOD/SCID mice. We also eventually found this cancer stem cell like population (BCRP1+/CD133+) in other types of cancer, even in a brain tumour patient sample with aggressive disease, but not in patient sample with good prognosis. Besides, the important finding in this study is that inhibition of cancer stem cell self renewal could reflex a decrease in resistance to chemotherapy. IC50 and percentage of resistant cells is reported after treatment with a stem cell self renewal inhibitor.

Keywords: BCRP1, ABCG2, ABC transporter family, EpCAM, DFFDA, long retaining labelling cells, Cancer stem cell, self renewal inhibition, asymmetric division, Pigmented epithelium derived factor (PEDF).
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