title: Characterization of subpopulation lacking both B-cell and plasma cell markers in Waldenstrom macroglobulinemia cell line.
abstract: Cancer cells with tumorigenic potential are limited to a small population known as cancer-initiating cells (CICs). To date, CICs have not been identified in non-Hodgkin's lymphomas. Here, we investigated a candidate of CICs of an indolent non-Hodgkin's lymphoma, Waldenstrom macroglobulinemia (WM), using WM cell line MWCL-1. WM tumor expresses both B-cell and plasma cell markers, CD20 and CD138. When stained with anti-CD20 and anti-CD138 antibodies, MWCL-1 cells were classified into three subpopulations: CD20⁻ CD138⁻, CD20⁺ CD138⁻, and CD20⁺ CD138⁺. When cultured, CD20⁻ CD138⁻ cells yielded all three subpopulations, but CD20⁺ cells did not yield CD20⁻ CD138⁻ cells. Higher reactive oxygen species (ROS) expelling and in vitro colony formation activities were detected in CD20⁻ CD138⁻ cells than in CD20⁺ CD138⁻ and CD20⁺ CD138⁺ cells. When cultured in the absence of serum or with anti-cancer drug, CD20⁻ CD138⁻ cells were resistant to apoptosis. In contrast, CD20⁺ CD138⁺ cells were vulnerable to apoptosis in the same condition. In fact, the immunohistochemical analysis with clinical samples revealed that tumor cells in apoptosis were CD138-positive. The production of all three subpopulations, the efficient ROS expelling and in vitro colony-forming activities, and the resistance to apoptosis suggested that the CD20⁻ CD138⁻ cell might be a candidate of CICs in WM.
authors.affiliation: Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Wada
authors.affiliation: Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Maosheng
authors.initials: M
authors.lastname: Zhan
authors.affiliation: Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Hori
authors.affiliation: Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Honma
authors.affiliation: Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Jun-ichiro
authors.initials: J
authors.lastname: Ikeda
authors.affiliation: Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Morii
mesh_terms: D018951:Antigens, CD20 / Q000378:metabolism*; D017209:Apoptosis; D001402:B-Lymphocytes / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000502:physiology; D005434:Flow Cytometry; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D053668:Syndecan-1 / Q000378:metabolism*; D008258:Waldenstrom Macroglobulinemia / Q000378:metabolism* / Q000473:pathology*
chemical_list: D018951:Antigens, CD20; D015415:Biomarkers; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D017382:Reactive Oxygen Species; C508241:SDC1 protein, human; D053668:Syndecan-1