Journal of Pathology and Translational Medicine

Original Articles

Senescent tumor cells in colorectal cancer are characterized by elevated enzymatic activity of complexes 1 and 2 in oxidative phosphorylation: 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; J Pathol Transl Med. 2023;57(6):305-314. Published online November 7, 2023; DOI: https://doi.org/10.4132/jptm.2023.10.09

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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.

Citations

Citations to this article as recorded by

Cellular Aging and Senescence in Cancer: A Holistic Review of Cellular Fate Determinants
Muhammad Tufail, Yu-Qi Huang, Jia-Ju Hu, Jie Liang, Cai-Yun He, Wen-Dong Wan, Can-Hua Jiang, Hong Wu, Ning Li
Aging and disease.2024;[Epub] CrossRef
Real-time assessment of relative mitochondrial ATP synthesis response against inhibiting and stimulating substrates (MitoRAISE)
Eun Sol Chang, Kyoung Song, Ji-Young Song, Minjung Sung, Mi-Sook Lee, Jung Han Oh, Ji-Yeon Kim, Yeon Hee Park, Kyungsoo Jung, Yoon-La Choi
Cancer & Metabolism.2024;[Epub] CrossRef

The Expression of Transforming Growth Factor-beta1 and alpha-Smooth Muscle Actin is Increased in the Human Myxomatous Valve.: Jeong Hwan Park, Ho Joong Youn, Jung Sook Yoon, Chul Soo Park, Soo Sung Oh, Woo Baek Chung, Jong Won Chung, Yun Seok Choi, Dong Hyun Lee, Yong Seog Oh, Wook Sung Chung, Soon Jo Hong, Youn Soo Lee, Sung Bo Sim, Sun Hee Lee; Korean J Pathol. 2009;43(2):152-156.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.2.152

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Abstract PDF

BACKGROUND
In vitro experimental studies have reported that transforming growth factor-beta1 (TGF-beta1) stimulates the production of alpha-smooth muscle actin (alpha-SMA) in porcine valves. However, the relation between TGF-beta1 and alpha-SMA in myxomatous valves has not been elucidated.
METHODS
We classified 27 subjects into two groups: 1) myxomatous group (M:F=11:12, mean age=55+/-15 years) and 2) rheumatic group (M:F=3:1, mean age=41+/-17 years) according to preoperative echocardiographic and postoperative histologic findings. Twenty-seven valve specimens from the patients who underwent valve replacement were obtained. Tissue samples were analyzed by immunohistochemistry for TGF-beta1 and alpha-SMA. The positively stained areas were measured using an image analysis program (Image Pro-Plus 4.5), and then the TGF-beta1 volume fraction (TGF-VF) and alpha-SMA volume fraction (alpha-SMA-VF) were calculated.
RESULTS
TGF-VF in myxomatous valves was higher than in rheumatic valves (2,759+/-2,294 vs 864+/-276, p=0.04). alpha-SMA-VF in myxomatous valves was higher than in rheumatic valves (4,122+/-2,275 vs 2,421+/-844, p=0.002). There was a significant correlation between TGF-beta1 and alpha-SMA in myxomatous valves (r=0.38, p=0.04). There was no significant correlation between TGF-beta1 and alpha-SMA in rheumatic valves (r=-0.50, p=0.67).
CONCLUSIONS
TGF-beta1 and alpha-SMA may be related to the pathogenesis of myxomatous valves. The activation of TGF-beta1 might increase the expression of alpha-SMA in human myxomatous valves.

Citations

Citations to this article as recorded by

Apoptosis and abundance of Bcl-2 family and transforming growth factor β1 signaling proteins in canine myxomatous mitral valves
Sirilak Surachetpong, Treenate Jiranantasak, Anudep Rungsipipat, E. Christopher Orton
Journal of Veterinary Cardiology.2013; 15(3): 171. CrossRef
Pathology, protein expression and signaling in myxomatous mitral valve degeneration: Comparison of dogs and humans
Heike Aupperle, Sirilak Disatian
Journal of Veterinary Cardiology.2012; 14(1): 59. CrossRef

Case Report

Ectopic Hamartomatous Thymoma: A Case Report along with a Review of the Literature Concerning the Histogenesis and New Nomenclature.: Sang Hee Seok, Dong Hyun Lee, Su Hwan Kang, Young Kyung Bae; Korean J Pathol. 2006;40(4):292-296.

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Abstract PDF: Ectopic hamartomatous thymoma (EHT) is a rare and distinctive benign neoplasm of the lower neck. We here report on a case of EHT arising in the suprasternal area of 47-year-old male patient. The well-circumscribed mass measured 7 x 6 x 4 cm and it predominantly had a solid gray-white cut surface. Microscopically, the tumor consisted of spindle cells, epithelial nests, and mature adipose tissue. The epithelial component was arranged in anastomosing cords, solid nests and variable-sized cysts that were lined by squamous or cuboidal epithelium. The spindle cells revealed the myoepithelial immunohistochemical phenotype. There was no obvious thymic differentiation nor was any normal thymic tissue observed in our case. We think that EHT needs to be reclassified with using different nomenclature to designate its origin and histology. Further, pathologists and clinicians should be aware of the existence of this tumor in the lower neck so as not to mistake it for high-grade sarcoma or spindle cell carcinoma.

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