Cargando…
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...
Autores principales: | , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784869478643793920 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9839411 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT chenchihjung calreticulinexpressioncontrolscellularredoxstemnessandradiosensitivitytofunctionasanoveladjuvantforradiotherapyinneuroblastoma AT huyachuan calreticulinexpressioncontrolscellularredoxstemnessandradiosensitivitytofunctionasanoveladjuvantforradiotherapyinneuroblastoma AT chienyueh calreticulinexpressioncontrolscellularredoxstemnessandradiosensitivitytofunctionasanoveladjuvantforradiotherapyinneuroblastoma AT huangweichieh calreticulinexpressioncontrolscellularredoxstemnessandradiosensitivitytofunctionasanoveladjuvantforradiotherapyinneuroblastoma AT wuchisheng calreticulinexpressioncontrolscellularredoxstemnessandradiosensitivitytofunctionasanoveladjuvantforradiotherapyinneuroblastoma AT tsaichungying calreticulinexpressioncontrolscellularredoxstemnessandradiosensitivitytofunctionasanoveladjuvantforradiotherapyinneuroblastoma AT linyanghsiang calreticulinexpressioncontrolscellularredoxstemnessandradiosensitivitytofunctionasanoveladjuvantforradiotherapyinneuroblastoma AT leemengshiue calreticulinexpressioncontrolscellularredoxstemnessandradiosensitivitytofunctionasanoveladjuvantforradiotherapyinneuroblastoma AT chienchianshiu calreticulinexpressioncontrolscellularredoxstemnessandradiosensitivitytofunctionasanoveladjuvantforradiotherapyinneuroblastoma AT yangyiping calreticulinexpressioncontrolscellularredoxstemnessandradiosensitivitytofunctionasanoveladjuvantforradiotherapyinneuroblastoma AT leemengchou calreticulinexpressioncontrolscellularredoxstemnessandradiosensitivitytofunctionasanoveladjuvantforradiotherapyinneuroblastoma AT tsengchungchih calreticulinexpressioncontrolscellularredoxstemnessandradiosensitivitytofunctionasanoveladjuvantforradiotherapyinneuroblastoma AT chihsiangcheng calreticulinexpressioncontrolscellularredoxstemnessandradiosensitivitytofunctionasanoveladjuvantforradiotherapyinneuroblastoma |