title: Cancer stem-like cells derived from chemoresistant tumors have a unique capacity to prime tumorigenic myeloid cells.
abstract: Resistance to anticancer therapeutics greatly affects the phenotypic and functional properties of tumor cells, but how chemoresistance contributes to the tumorigenic activities of cancer stem-like cells remains unclear. In this study, we found that a characteristic of cancer stem-like cells from chemoresistant tumors (CSC-R) is the ability to produce a variety of proinflammatory cytokines and to generate M2-like immunoregulatory myeloid cells from CD14(+) monocytes. Furthermore, we identified the IFN-regulated transcription factor IRF5 as a CSC-R-specific factor critical for promoting M-CSF production and generating tumorigenic myeloid cells. Importantly, myeloid cells primed with IRF5(+) CSC-R facilitate the tumorigenic and stem cell activities of bulk tumors. Importantly, the activation of IRF5/M-CSF pathways in tumor cells were correlated with the number of tumor-associated CSF1 receptor(+) M2 macrophages in patients with non-small lung cancer. Collectively, our findings show how chemoresistance affects the properties of CSCs in their niche microenvironments.
authors.affiliation: Authors' Affiliations: Research Center for Infection-Associated Cancer, Institute for Genetic Medicine, Hokkaido University; Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo; and Center for AIDS research, Kumamoto University, Kumamoto, Japan.
authors.forename: Tsunaki
authors.initials: T
authors.lastname: Yamashina
authors.affiliation: Authors' Affiliations: Research Center for Infection-Associated Cancer, Institute for Genetic Medicine, Hokkaido University; Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo; and Center for AIDS research, Kumamoto University, Kumamoto, Japan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Baghdadi
authors.affiliation: Authors' Affiliations: Research Center for Infection-Associated Cancer, Institute for Genetic Medicine, Hokkaido University; Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo; and Center for AIDS research, Kumamoto University, Kumamoto, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yoneda
authors.affiliation: Authors' Affiliations: Research Center for Infection-Associated Cancer, Institute for Genetic Medicine, Hokkaido University; Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo; and Center for AIDS research, Kumamoto University, Kumamoto, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kinoshita
authors.affiliation: Authors' Affiliations: Research Center for Infection-Associated Cancer, Institute for Genetic Medicine, Hokkaido University; Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo; and Center for AIDS research, Kumamoto University, Kumamoto, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Suzu
authors.affiliation: Authors' Affiliations: Research Center for Infection-Associated Cancer, Institute for Genetic Medicine, Hokkaido University; Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo; and Center for AIDS research, Kumamoto University, Kumamoto, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Dosaka-Akita
authors.affiliation: Authors' Affiliations: Research Center for Infection-Associated Cancer, Institute for Genetic Medicine, Hokkaido University; Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo; and Center for AIDS research, Kumamoto University, Kumamoto, Japan Jinushi@igm.hokudai.ac.jp.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Jinushi
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D045325:HCT116 Cells; D064593:Heterografts; D006801:Humans; D050835:Interferon Regulatory Factors / Q000378:metabolism; D008264:Macrophages / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009000:Monocytes / Q000473:pathology; D022423:Myeloid Cells / Q000378:metabolism / Q000473:pathology*; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D055153:Stem Cell Niche; D015854:Up-Regulation
chemical_list: C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors