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Calreticulin Expression Controls Cellular Redox, Stemness, and Radiosensitivity to Function as a Novel Adjuvant for Radiotherapy in Neuroblastoma

Radiotherapy (RT) is currently only used in children with high-risk neuroblastoma (NB) due to concerns of long-term side effects as well as lack of effective adjuvant. Calreticulin (CALR) has served distinct physiological roles in cancer malignancies; nonetheless, impact of radiation on chaperones a...

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Autores principales: Chen, Chih-Jung, Hu, Ya-Chuan, Chien, Yueh, Huang, Wei-Chieh, Wu, Chi-Sheng, Tsai, Chung-Ying, Lin, Yang-Hsiang, Lee, Meng-Shiue, Chien, Chian-Shiu, Yang, Yi-Ping, Lee, Meng-Chou, Tseng, Chung-Chih, Chi, Hsiang-Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839411/
https://www.ncbi.nlm.nih.gov/pubmed/36644580
http://dx.doi.org/10.1155/2023/8753309
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author Chen, Chih-Jung
Hu, Ya-Chuan
Chien, Yueh
Huang, Wei-Chieh
Wu, Chi-Sheng
Tsai, Chung-Ying
Lin, Yang-Hsiang
Lee, Meng-Shiue
Chien, Chian-Shiu
Yang, Yi-Ping
Lee, Meng-Chou
Tseng, Chung-Chih
Chi, Hsiang-Cheng
author_facet Chen, Chih-Jung
Hu, Ya-Chuan
Chien, Yueh
Huang, Wei-Chieh
Wu, Chi-Sheng
Tsai, Chung-Ying
Lin, Yang-Hsiang
Lee, Meng-Shiue
Chien, Chian-Shiu
Yang, Yi-Ping
Lee, Meng-Chou
Tseng, Chung-Chih
Chi, Hsiang-Cheng
author_sort Chen, Chih-Jung
collection PubMed
description Radiotherapy (RT) is currently only used in children with high-risk neuroblastoma (NB) due to concerns of long-term side effects as well as lack of effective adjuvant. Calreticulin (CALR) has served distinct physiological roles in cancer malignancies; nonetheless, impact of radiation on chaperones and molecular roles they play remains largely unknown. In present study, we systemically analyzed correlation between CALR and NB cells of different malignancies to investigate potential role of CALR in mediating radioresistance of NB. Our data revealed that more malignant NB cells are correlated to lower CALR expression, greater radioresistance, and elevated stemness as indicated by colony- and neurospheroid-forming abilities and vice versa. Of note, manipulating CALR expression in NB cells of varying endogenous CALR expression manifested changes in not only stemness but also radioresistant properties of those NB cells. Further, CALR overexpression resulted in greatly enhanced ROS and led to increased secretion of proinflammatory cytokines. Importantly, growth of NB tumors was significantly hampered by CALR overexpression and was synergistically ablated when RT was also administered. Collectively, our current study unraveled a new notion of utilizing CALR expression in malignant NB to diminish cancer stemness and mitigate radioresistance to achieve favorable therapeutic outcome for NB.
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spelling pubmed-98394112023-01-14 Calreticulin Expression Controls Cellular Redox, Stemness, and Radiosensitivity to Function as a Novel Adjuvant for Radiotherapy in Neuroblastoma Chen, Chih-Jung Hu, Ya-Chuan Chien, Yueh Huang, Wei-Chieh Wu, Chi-Sheng Tsai, Chung-Ying Lin, Yang-Hsiang Lee, Meng-Shiue Chien, Chian-Shiu Yang, Yi-Ping Lee, Meng-Chou Tseng, Chung-Chih Chi, Hsiang-Cheng Oxid Med Cell Longev Research Article Radiotherapy (RT) is currently only used in children with high-risk neuroblastoma (NB) due to concerns of long-term side effects as well as lack of effective adjuvant. Calreticulin (CALR) has served distinct physiological roles in cancer malignancies; nonetheless, impact of radiation on chaperones and molecular roles they play remains largely unknown. In present study, we systemically analyzed correlation between CALR and NB cells of different malignancies to investigate potential role of CALR in mediating radioresistance of NB. Our data revealed that more malignant NB cells are correlated to lower CALR expression, greater radioresistance, and elevated stemness as indicated by colony- and neurospheroid-forming abilities and vice versa. Of note, manipulating CALR expression in NB cells of varying endogenous CALR expression manifested changes in not only stemness but also radioresistant properties of those NB cells. Further, CALR overexpression resulted in greatly enhanced ROS and led to increased secretion of proinflammatory cytokines. Importantly, growth of NB tumors was significantly hampered by CALR overexpression and was synergistically ablated when RT was also administered. Collectively, our current study unraveled a new notion of utilizing CALR expression in malignant NB to diminish cancer stemness and mitigate radioresistance to achieve favorable therapeutic outcome for NB. Hindawi 2023-01-06 /pmc/articles/PMC9839411/ /pubmed/36644580 http://dx.doi.org/10.1155/2023/8753309 Text en Copyright © 2023 Chih-Jung Chen et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Chen, Chih-Jung
Hu, Ya-Chuan
Chien, Yueh
Huang, Wei-Chieh
Wu, Chi-Sheng
Tsai, Chung-Ying
Lin, Yang-Hsiang
Lee, Meng-Shiue
Chien, Chian-Shiu
Yang, Yi-Ping
Lee, Meng-Chou
Tseng, Chung-Chih
Chi, Hsiang-Cheng
Calreticulin Expression Controls Cellular Redox, Stemness, and Radiosensitivity to Function as a Novel Adjuvant for Radiotherapy in Neuroblastoma
title Calreticulin Expression Controls Cellular Redox, Stemness, and Radiosensitivity to Function as a Novel Adjuvant for Radiotherapy in Neuroblastoma
title_full Calreticulin Expression Controls Cellular Redox, Stemness, and Radiosensitivity to Function as a Novel Adjuvant for Radiotherapy in Neuroblastoma
title_fullStr Calreticulin Expression Controls Cellular Redox, Stemness, and Radiosensitivity to Function as a Novel Adjuvant for Radiotherapy in Neuroblastoma
title_full_unstemmed Calreticulin Expression Controls Cellular Redox, Stemness, and Radiosensitivity to Function as a Novel Adjuvant for Radiotherapy in Neuroblastoma
title_short Calreticulin Expression Controls Cellular Redox, Stemness, and Radiosensitivity to Function as a Novel Adjuvant for Radiotherapy in Neuroblastoma
title_sort calreticulin expression controls cellular redox, stemness, and radiosensitivity to function as a novel adjuvant for radiotherapy in neuroblastoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839411/
https://www.ncbi.nlm.nih.gov/pubmed/36644580
http://dx.doi.org/10.1155/2023/8753309
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