Senescent tumor cells in colorectal cancer are characterized by elevated enzymatic activity of complexes 1 and 2 in oxidative phosphorylation.

IF 1.7 Q3 PATHOLOGY Journal of Pathology and Translational Medicine Pub Date : 2023-11-01 Epub Date: 2023-11-07 DOI:10.4132/jptm.2023.10.09
Jun Sang Shin, Tae-Gyu Kim, Young Hwa Kim, So Yeong Eom, So Hyun Park, Dong Hyun Lee, Tae Jun Park, Soon Sang Park, Jang-Hee Kim
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Abstract

Background: Cellular senescence is defined as an irreversible cell cycle arrest caused by various internal and external insults. While the metabolic dysfunction of senescent cells in normal tissue is relatively well-established, there is a lack of information regarding the metabolic features of senescent tumor cells.

Methods: Publicly available single-cell RNA-sequencing data from the GSE166555 and GSE178341 datasets were utilized to investigate the metabolic features of senescent tumor cells. To validate the single-cell RNA-sequencing data, we performed senescence-associated β-galactosidase (SA-β-Gal) staining to identify senescent tumor cells in fresh frozen colorectal cancer tissue. We also evaluated nicotinamide adenine dinucleotide dehydrogenase-tetrazolium reductase (NADH-TR) and succinate dehydrogenase (SDH) activity using enzyme histochemical methods and compared the staining with SA-β-Gal staining. MTT assay was performed to reveal the complex 1 activity of the respiratory chain in in-vitro senescence model.

Results: Single-cell RNA-sequencing data revealed an upregulation in the activity of complexes 1 and 2 in oxidative phosphorylation, despite overall mitochondrial dysfunction in senescent tumor cells. Both SA-β-Gal and enzyme histochemical staining using fresh frozen colorectal cancer tissues indicated a high correlation between SA-β-Gal positivity and NADH-TR/SDH staining positivity. MTT assay showed that senescent colorectal cancer cells exhibit higher absorbance in 600 nm wavelength.

Conclusions: Senescent tumor cells exhibit distinct metabolic features, characterized by upregulation of complexes 1 and 2 in the oxidative phosphorylation pathway. NADH-TR and SDH staining represent efficient methods for detecting senescent tumor cells in colorectal cancer.

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结直肠癌癌症中的衰老肿瘤细胞的特征是复合物1和2在氧化磷酸化中的酶活性升高。
背景:细胞衰老被定义为由各种内部和外部损伤引起的不可逆的细胞周期停滞。虽然正常组织中衰老细胞的代谢功能障碍相对公认,但缺乏关于衰老肿瘤细胞代谢特征的信息。方法:利用来自GSE166555和GSE178341数据集的公开可用的单细胞RNA测序数据来研究衰老肿瘤细胞的代谢特征。为了验证单细胞RNA序列数据,我们进行了衰老相关β-半乳糖苷酶(SA-β-Gal)染色,以鉴定新鲜冷冻结直肠癌癌症组织中的衰老肿瘤细胞。我们还用酶组织化学方法评估了烟酰胺腺嘌呤二核苷酸脱氢酶四氮唑还原酶(NADH-TR)和琥珀酸脱氢酶(SDH)的活性,并将其与SA-β-Gal染色进行了比较。MTT法检测体外衰老模型中呼吸链复合体1的活性。结果:单细胞RNA测序数据显示,尽管衰老肿瘤细胞中存在线粒体功能障碍,但复合物1和2在氧化磷酸化中的活性上调。用新鲜冷冻癌症组织进行的SA-β-Gal和酶组织化学染色表明,SA-β-Gal阳性与NADH-TR/SDH染色阳性之间具有高度相关性。MTT检测显示衰老的癌症细胞在600nm波长下表现出较高的吸光度。结论:衰老的肿瘤细胞表现出不同的代谢特征,其特征是氧化磷酸化途径中复合物1和2的上调。NADH-TR和SDH染色是检测癌症衰老肿瘤细胞的有效方法。
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来源期刊
CiteScore
5.00
自引率
4.20%
发文量
45
审稿时长
14 weeks
期刊介绍: The Journal of Pathology and Translational Medicine is an open venue for the rapid publication of major achievements in various fields of pathology, cytopathology, and biomedical and translational research. The Journal aims to share new insights into the molecular and cellular mechanisms of human diseases and to report major advances in both experimental and clinical medicine, with a particular emphasis on translational research. The investigations of human cells and tissues using high-dimensional biology techniques such as genomics and proteomics will be given a high priority. Articles on stem cell biology are also welcome. The categories of manuscript include original articles, review and perspective articles, case studies, brief case reports, and letters to the editor.
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