title: Identification of cancer stem cell markers in human malignant mesothelioma cells.
abstract: 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.
authors.affiliation: Division of Clinical Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Farhana Ishrat
authors.initials: FI
authors.lastname: Ghani
authors.forename: Hiroto
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Iwata
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Okamoto
authors.forename: Keisuke
authors.initials: K
authors.lastname: Aoe
authors.forename: Kazunori
authors.initials: K
authors.lastname: Okabe
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Mimura
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Fujimoto
authors.forename: Takumi
authors.initials: T
authors.lastname: Kishimoto
authors.forename: Taketo
authors.initials: T
authors.lastname: Yamada
authors.forename: C Wilson
authors.initials: CW
authors.lastname: Xu
authors.forename: Chikao
authors.initials: C
authors.lastname: Morimoto
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D051927:CD24 Antigen / Q000378:metabolism*; D045744:Cell Line, Tumor; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008654:Mesothelioma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D060245:Tetraspanin 29
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D051927:CD24 Antigen; C497889:CD24 protein, human; C554869:CD9 protein, human; C554870:Cd9 protein, mouse; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4