TY - JOUR
T1 - CD49f-positive cell population efficiently enriches colon cancer-initiating cells
AU - Haraguchi, Naotsugu
AU - Ishii, Hideshi
AU - Mimori, Koshi
AU - Ohta, Katsuya
AU - Uemura, Mamoru
AU - Nishimura, Junichi
AU - Hata, Taishi
AU - Takemasa, Ichiro
AU - Mizushima, Tsunekazu
AU - Yamamoto, Hirofumi
AU - Doki, Yuichiro
AU - Mori, Masaki
PY - 2013/8
Y1 - 2013/8
N2 - Cancer stem cells (CSCs) also known as cancer-initiating cells (CICs) show high tumorigenic activity and high chemo- and radiation resistance. It is, therefore, important to identify CSCs reliably to develop novel curative cancer treatments. In this study, we re-evaluated CSC markers of colorectal cancer for their cellular differentiation and tumorigenic activity, with the aim to identify reliable CSC markers. The rates of change in CD44, CD133, CD166, CD24, CD49f and CXCR4 expression during sodium butyrate (NaBT)-induced cell differentiation were assessed in HT29 and Caco2 colon cancer cell lines. Expression levels of target markers were assessed in clinical CRC samples. Tumorigenic activity was assessed on isolated cell fractions identified by multicolor flow cytometric analysis. In the cell differentiation assay, the average percent change was higher in CD44 (-98.2%) and CD49f (-74.4%) compared to CD133 (-17.9%) and CD166 (-49.4%). Expression of CD24 and CXCR4 appeared random in HT29 and Caco2. Expression of CD44, CD49f, CD133 and CD166 was confirmed in all four clinical CRC samples. Limiting dilution assay of CD44- and CD133-expressing cells revealed that only the CD133+CD44+ population possessed tumorigenic activity. Tumorigenesis was not affected by CD166 expression. Highly tumorigenic cells could be enriched in samples with higher CD49f expression; CD49f+ cells showed high tumorigenesis, whereas CD133+ and CD44+ cells that were negative for CD49f exhibited no tumorigenic activity. Multicolor analysis revealed that CD49f+ cells localized in CD44+ and CD133+ cell fractions. These findings demonstrated that CD49f is an important marker for identifying colorectal CSCs and suggest that the CD49f+ cell fraction may be the best candidate for colorectal CSCs.
AB - Cancer stem cells (CSCs) also known as cancer-initiating cells (CICs) show high tumorigenic activity and high chemo- and radiation resistance. It is, therefore, important to identify CSCs reliably to develop novel curative cancer treatments. In this study, we re-evaluated CSC markers of colorectal cancer for their cellular differentiation and tumorigenic activity, with the aim to identify reliable CSC markers. The rates of change in CD44, CD133, CD166, CD24, CD49f and CXCR4 expression during sodium butyrate (NaBT)-induced cell differentiation were assessed in HT29 and Caco2 colon cancer cell lines. Expression levels of target markers were assessed in clinical CRC samples. Tumorigenic activity was assessed on isolated cell fractions identified by multicolor flow cytometric analysis. In the cell differentiation assay, the average percent change was higher in CD44 (-98.2%) and CD49f (-74.4%) compared to CD133 (-17.9%) and CD166 (-49.4%). Expression of CD24 and CXCR4 appeared random in HT29 and Caco2. Expression of CD44, CD49f, CD133 and CD166 was confirmed in all four clinical CRC samples. Limiting dilution assay of CD44- and CD133-expressing cells revealed that only the CD133+CD44+ population possessed tumorigenic activity. Tumorigenesis was not affected by CD166 expression. Highly tumorigenic cells could be enriched in samples with higher CD49f expression; CD49f+ cells showed high tumorigenesis, whereas CD133+ and CD44+ cells that were negative for CD49f exhibited no tumorigenic activity. Multicolor analysis revealed that CD49f+ cells localized in CD44+ and CD133+ cell fractions. These findings demonstrated that CD49f is an important marker for identifying colorectal CSCs and suggest that the CD49f+ cell fraction may be the best candidate for colorectal CSCs.
UR - http://www.scopus.com/inward/record.url?scp=84879632446&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879632446&partnerID=8YFLogxK
U2 - 10.3892/ijo.2013.1955
DO - 10.3892/ijo.2013.1955
M3 - Article
C2 - 23708747
AN - SCOPUS:84879632446
VL - 43
SP - 425
EP - 430
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 2
ER -