title: Requirement of CXCL12-CXCR7 signaling for CD20(-) CD138(-) double-negative population in lymphoplasmacytic lymphoma.
abstract: Cancer cells with tumorigenic potential are limited to a small subpopulation known as cancer-initiating cells (CICs). Recently we investigated a candidate of CICs of lymphoplasmacytic lymphoma (LPL), which is positive for both B-cell marker CD20 and plasma-cell marker CD138. We reported that the subpopulation of CD20(-) CD138(-) phenotype, in which both markers were negative was a candidate of CICs in LPL using LPL cell line, MWCL-1. CICs are known to be plastic under stressed condition, in which non-CICs are changed to CICs. In the present study, we investigated the plasticity of CICs of LPL, and found that hypoxia induced the conversion of CD20(+) CD138(-) to CD20(-) CD138(-) phenotype. We then searched for markers preferentially expressed in CD20(-) CD138(-) subpopulation, and the chemokine receptor CXCR7 was isolated. When cultured with CXCL12, a ligand of CXCR7, the number of CD20(-) CD138(-) cells increased in a time- and dose-dependent manner. In addition, hypoxia enhanced the expression level of CXCL12 in MWCL-1. In clinical samples of LPL, a few tumor cells expressed CXCR7, in which CD20 expression was not detected. These results indicated that hypoxia and CXCL12-CXCR7 axis appeared to be advantageous microenvironments to CD20(-) CD138(-) cells.
authors.affiliation: Department of Pathology (C3), Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Wada
authors.affiliation: Department of Pathology (C3), Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Jun-Ichiro
authors.initials: J
authors.lastname: Ikeda
authors.affiliation: Department of Pathology (C3), Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nojima
authors.affiliation: Department of Pathology (C3), Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Tahara
authors.affiliation: Department of Pathology (C3), Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ohshima
authors.affiliation: DNA Chip Development Center, RIMD, Osaka University, Suita, Osaka, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Okuzaki
authors.affiliation: Department of Pathology (C3), Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Morii
mesh_terms: D000368:Aged; D018951:Antigens, CD20 / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000473:pathology; D054387:Receptors, CXCR / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D053668:Syndecan-1 / Q000378:metabolism; D059016:Tumor Microenvironment / Q000276:immunology; D015854:Up-Regulation; D008258:Waldenstrom Macroglobulinemia / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: C501896:ACKR3 protein, human; D018951:Antigens, CD20; D014408:Biomarkers, Tumor; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D054387:Receptors, CXCR; C508241:SDC1 protein, human; D053668:Syndecan-1