title: Target irradiation induced bystander effects between stem-like and non stem-like cancer cells.
abstract: Tumors are heterogeneous in nature and consist of multiple cell types. Among them, cancer stem-like cells (CSCs) are suggested to be the principal cause of tumor metastasis, resistance and recurrence. Therefore, understanding the behavior of CSCs in direct and indirect irradiations is crucial for clinical radiotherapy. Here, the CSCs and their counterpart non stem-like cancer cells (NSCCs) in human HT1080 fibrosarcoma cell line were sorted and labeled, then the two cell subtypes were mixed together and chosen separately to be irradiated via a proton microbeam. The radiation-induced bystander effect (RIBE) between the CSCs and NSCCs was measured by imaging 53BP1 foci, a widely used indicator for DNA double strand break (DSB). CSCs were found to be less active than NSCCs in both the generation and the response of bystander signals. Moreover, the nitric oxide (NO) scavenger c-PTIO can effectively alleviate the bystander effect in bystander NSCCs but not in bystander CSCs, indicating a difference of the two cell subtypes in NO signal response. To our knowledge, this is the first report shedding light on the RIBE between CSCs and NSCCs, which might contribute to a further understanding of the out-of-field effect in cancer radiotherapy.
authors.affiliation: State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871 P.R. China; Space Radiation Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Space Radiation Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555, Japan; Department of Technical Support and Development, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555, Japan.
authors.forename: Alisa
authors.initials: A
authors.lastname: Kobayashi
authors.affiliation: Department of Technical Support and Development, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Maeda
authors.affiliation: State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871 P.R. China.
authors.forename: Qibin
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Technical Support and Development, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Oikawa
authors.affiliation: State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871 P.R. China; Space Radiation Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555, Japan. Electronic address: gen.yang@pku.edu.cn.
authors.forename: Gen
authors.initials: G
authors.lastname: Yang
authors.affiliation: Space Radiation Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555, Japan; Department of Technical Support and Development, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555, Japan. Electronic address: tkonishi@nirs.go.jp.
authors.forename: Teruaki
authors.initials: T
authors.lastname: Konishi
authors.affiliation: Space Radiation Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555, Japan; Department of Technical Support and Development, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Uchihori
authors.affiliation: Space Radiation Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555, Japan; Center for Radiological Research, Columbia, VC11-205, 630 West 168th Street, New York, NY 10032, United States.
authors.forename: Tom K
authors.initials: TK
authors.lastname: Hei
authors.affiliation: State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871 P.R. China.
authors.forename: Yugang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D024201:Bystander Effect; D045744:Cell Line, Tumor; D006801:Humans; D014411:Neoplastic Stem Cells / Q000502:physiology / Q000528:radiation effects*; D009569:Nitric Oxide / Q000502:physiology; D011836:Radiation Tolerance
chemical_list: D009569:Nitric Oxide; D000444:Aldehyde Dehydrogenase
keywords: 53BP1; Cancer stem-like cells (CSCs); Proton microbeam; Radiation-induced Bystander Effect (RIBE); c-PTIO