title: Tracking and Finding Slow-Proliferating/Quiescent Cancer Stem Cells with Fluorescent Nanodiamonds.
abstract: Quiescent cancer stem cells (CSCs) have long been considered to be a source of tumor initiation. However, identification and isolation of these cells have been hampered by the fact that commonly used fluorescent markers are not sufficiently stable, both chemically and photophysically, to allow tracking over an extended period of time. Here, it is shown that fluorescent nanodiamonds (FNDs) are well suited for this application. Genotoxicity tests of FNDs with comet and micronucleus assays for human fibroblasts and breast cancer cells indicate that the nanoparticles neither cause DNA damage nor impair cell growth. Using AS-B145-1R breast cancer cells as the model cell line for CSC, it is found that the FND labeling outperforms 5-ethynyl-2'-deoxyuridine (EdU) and carboxyfluorescein diacetate succinimidyl ester (CFSE) in regards to its long-term tracking capability (>20 d). Moreover, through a quantification of their stem cell activity by measuring mammosphere-forming efficiencies (MFEs) and self-renewal rates, the FND-positive cells are identified to have an MFE twice as high as that of the FND-negative cells isolated from the same dissociated mammospheres. Thus, the nanoparticle-based labeling technique provides an effective new tool for tracking and finding slow-proliferating/quiescent CSCs in cancer research.
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, 106, Taiwan.|Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan.|Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan, 333, Taiwan.|Taiwan International Graduate Program-Chemical Biology and Molecular Biophysics, Academia Sinica, Taipei, 115, Taiwan.
authors.forename: Hsin-Hung
authors.initials: HH
authors.lastname: Lin
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, 106, Taiwan.|Department of Chemistry, National Taiwan University, Taipei, 106, Taiwan.
authors.forename: Hsiao-Wen
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan.|Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan, 333, Taiwan.
authors.forename: Ruey-Jen
authors.initials: RJ
authors.lastname: Lin
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, 106, Taiwan.|Department of Chemistry, National Taiwan University, Taipei, 106, Taiwan.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Huang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Liao
authors.affiliation: Department of Chemistry, National Taiwan University, Taipei, 106, Taiwan.
authors.forename: Yit-Tsong
authors.initials: YT
authors.lastname: Chen
authors.affiliation: Department of Chemistry, National Taiwan University, Taipei, 106, Taiwan.
authors.forename: Jim-Min
authors.initials: JM
authors.lastname: Fang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan.
authors.forename: Te-Chang
authors.initials: TC
authors.lastname: Lee
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan.|Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan, 333, Taiwan.|Department of Pediatrics, University of California, San Diego, La Jolla, CA, 92093, USA.
authors.forename: Alice L
authors.initials: AL
authors.lastname: Yu
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, 106, Taiwan.
authors.forename: Huan-Cheng
authors.initials: HC
authors.lastname: Chang
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D058948:Cell Tracking / Q000379:methods*; D020552:Comet Assay; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005434:Flow Cytometry; D005453:Fluorescence; D006801:Humans; D018613:Microscopy, Confocal; D009153:Mutagens / Q000633:toxicity; D058612:Nanodiamonds / Q000737:chemistry*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D018874:Spheroids, Cellular / Q000187:drug effects / Q000473:pathology
chemical_list: D009153:Mutagens; D058612:Nanodiamonds
keywords: cancers; diamonds; fluorescence imaging; nanoparticles; stem cells