RRC ID 56592
著者 Shimamura M, Yamamoto K, Kurashige T, Nagayama Y.
タイトル Intracellular redox status controls spherogenicity, an in vitro cancer stem cell marker, in thyroid cancer cell lines.
ジャーナル Exp Cell Res
Abstract Cancer stem cells (CSCs), a small fraction of a tumor mass, are proposed to be highly crucial for cancer initiation, recurrence and metastasis. We have recently found that aldehyde dehydrogenase (ALDH) 1A3 is a CSC marker in some thyroid cancer cell lines, whose functional activity is, however, not relevant for thyroid cancer stemness. Since previous studies on malignancies in other organs suggest that intracellular reactive oxygen species (ROS) might be a functional and targetable CSC marker, the present study was conducted to elucidate the significance of ROS as a functional CSC marker in thyroid cancer cell lines. We first found that ROS levels controlled spherogenicity; that is, ROSlow cells were more spherogenic than ROShigh cells. However, unlike typical CSCs in other cancers, CSC-like ROSlow cells in thyroid cancer cells were plastic and were not accompanied by de-differentiation status (i.e., expression of stemness markers/thyroid-specific transcription factors) or chemo-/radio-resistance. The lower levels of ROS were functionally critical because a forced increase in ROS levels by L-buthionine-S,R-sulfoximine, an inhibitor of glutathione (GSH) synthesis, and irradiation suppressed spherogenicity. ROS levels were also correlated with the number of double strand DNA breaks determined by 53BP1 staining. Lower ROS levels appear to be a result of decreased mitochondrial oxidative phosphorylation and elevated GSH contents. Given the importance of CSC-targeted therapy for achieving long-term disease eradication by exhausting self-renewal and growth potential of cancer tissues, ROS may be a good candidate for CSC-targeted therapy in thyroid cancer.
巻・号 370(2)
ページ 699-707
公開日 2018-9-15
DOI 10.1016/j.yexcr.2018.07.036
PII S0014-4827(18)30570-6
PMID 30053445
MeSH Aldehyde Dehydrogenase / metabolism Cell Line, Tumor Cytoplasm / metabolism Humans Intracellular Space / metabolism Neoplastic Stem Cells / metabolism* Reactive Oxygen Species / metabolism* Thyroid Gland / metabolism* Thyroid Neoplasms / pathology*
IF 3.329
引用数 5
リソース情報
ヒト・動物細胞 8505C(RCB2103)