Characterization of Lin−ALDHbright population using Ehrlich ascites tumor cells in mice

• Published in: Tumor biology Vol. 35; no. 10; pp. 10363 - 10373
• Main Authors: Yalçintepe, Leman, Altinel, Pinar, Albeniz, Işil, Yilmaz, Abdullah, Nurten, Rustem
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-10-2014
• Subjects: Biomedical and Life Sciences; Biomedicine; Cancer Research; Research Article; Cancer stem cell; Ehrlich ascites tumor; ALDH; Drug resistance; Stem cell
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-014-2352-8

Cancer stem cells (CSCs)/tumor initiating cells have been shown to exist in recent studies; however, it is challenging to isolate these cells. The latest evidence suggests that elevated aldehyde dehydrogenase (ALDH) activity is a hallmark of CSCs. In this study, mice implanted with Ehrlich ascites tumor (EAT) cells were used to isolate cancer stem cells. Femoral bone marrow aspirations were performed 15 days after the injection of EAT cells and Lin
−
ALDH
bright
and Lin
−
ALDH
low
cell populations were isolated. Lin
−
ALDH
bright
cells isolated from EAT-bearing mice accounted for 11.08 ± 10.52 % of all the Lin
−
cell population. Analysis of hematopoietic stem cell markers showed that Sca-1, c-kit, and CD38 were expressed higher in the Lin
−
ALDH
bright
population compared with Lin
−
ALDH
low
. The Lin
−
ALDH
bright
population expressed P-glycoprotein, a product of the multidrug resistance (MDR) gene. P-gp activity measured by rhodamine 123 (Rh123) and blocked by verapamil. Among the cells treated with doxorubicin for 48 h, the Lin
−
ALDH
bright
cell groups were more resistant and had higher overexpression of Bcl-2 protein than Lin
−
ALDH
low
.