TY - JOUR
T1 - Identification of cancer stem cell markers in human malignant mesothelioma cells
AU - Ghani, Farhana Ishrat
AU - Yamazaki, Hiroto
AU - Iwata, Satoshi
AU - Okamoto, Toshihiro
AU - Aoe, Keisuke
AU - Okabe, Kazunori
AU - Mimura, Yusuke
AU - Fujimoto, Nobukazu
AU - Kishimoto, Takumi
AU - Yamada, Taketo
AU - Xu, C. Wilson
AU - Morimoto, Chikao
PY - 2011/1/14
Y1 - 2011/1/14
N2 - Malignant mesothelioma (MM) is an aggressive and therapy-resistant neoplasm arising from the pleural mesothelial cells and usually associated with long-term asbestos exposure. Recent studies suggest that tumors contain cancer stem cells (CSCs) and their stem cell characteristics are thought to confer therapy-resistance. However, whether MM cell has any stem cell characteristics is not known. To understand the molecular basis of MM, we first performed serial transplantation of surgical samples into NOD/SCID mice and established new cell lines. Next, we performed marker analysis of the MM cell lines and found that many of them contain SP cells and expressed several putative CSC markers such as CD9, CD24, and CD26. Interestingly, expression of CD26 closely correlated with that of CD24 in some cases. Sorting and culture assay revealed that SP and CD24+ cells proliferated by asymmetric cell division-like manner. In addition, CD9+ and CD24+ cells have higher potential to generate spheroid colony than negative cells in the stem cell medium. Moreover, these marker-positive cells have clear tendency to generate larger tumors in mouse transplantation assay. Taken together, our data suggest that SP, CD9, CD24, and CD26 are CSC markers of MM and could be used as novel therapeutic targets.
AB - Malignant mesothelioma (MM) is an aggressive and therapy-resistant neoplasm arising from the pleural mesothelial cells and usually associated with long-term asbestos exposure. Recent studies suggest that tumors contain cancer stem cells (CSCs) and their stem cell characteristics are thought to confer therapy-resistance. However, whether MM cell has any stem cell characteristics is not known. To understand the molecular basis of MM, we first performed serial transplantation of surgical samples into NOD/SCID mice and established new cell lines. Next, we performed marker analysis of the MM cell lines and found that many of them contain SP cells and expressed several putative CSC markers such as CD9, CD24, and CD26. Interestingly, expression of CD26 closely correlated with that of CD24 in some cases. Sorting and culture assay revealed that SP and CD24+ cells proliferated by asymmetric cell division-like manner. In addition, CD9+ and CD24+ cells have higher potential to generate spheroid colony than negative cells in the stem cell medium. Moreover, these marker-positive cells have clear tendency to generate larger tumors in mouse transplantation assay. Taken together, our data suggest that SP, CD9, CD24, and CD26 are CSC markers of MM and could be used as novel therapeutic targets.
KW - CD24
KW - CD26
KW - CD9
KW - Cancer stem cells
KW - Malignant mesothelioma
KW - Side population
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U2 - 10.1016/j.bbrc.2010.12.054
DO - 10.1016/j.bbrc.2010.12.054
M3 - Article
C2 - 21163253
AN - SCOPUS:78651367358
VL - 404
SP - 735
EP - 742
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -