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: Hsin-Hung Lin, Hsiao-Wen Lee, Ruey-Jen Lin, Chih-Wei Huang, Yi-Chun Liao, Yit-Tsong Chen, Jim-Min Fang, Te-Chang Lee, Alice L Yu, Huan-Cheng Chang
• Journal: Small (Weinheim an der Bergstrasse, Germany) (Small) Vol. 11 Issue 34 Pg. 4394-402 (Sep 09 2015) ISSN: 1613-6829 [Electronic] Germany
• PMID: 26077637 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Mutagens
• Nanodiamonds

Topics

• Cell Cycle (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cell Tracking (methods)
• Comet Assay
• Fibroblasts (cytology, drug effects)
• Flow Cytometry
• Fluorescence
• Humans
• Microscopy, Confocal
• Mutagens (toxicity)
• Nanodiamonds (chemistry)
• Neoplastic Stem Cells (drug effects, pathology)
• Spheroids, Cellular (drug effects, pathology)