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αV Integrin Induces Multicellular Radioresistance in Human Nasopharyngeal Carcinoma via Activating SAPK/JNK Pathway

BACKGROUND: Tumor cells acquire the capacity of resistance to chemotherapy or radiotherapy via cell–matrix and cell–cell crosstalk. Integrins are the most important cell adhesion molecules, in which αV integrin mainly mediating the tight contact between tumor cells. METHODOLOGY/PRINCIPAL FINDINGS: T...

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Detalles Bibliográficos
Autores principales: Ou, Juanjuan, Luan, Wei, Deng, Jia, Sa, Rina, Liang, Houjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374839/
https://www.ncbi.nlm.nih.gov/pubmed/22719931
http://dx.doi.org/10.1371/journal.pone.0038737
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author Ou, Juanjuan
Luan, Wei
Deng, Jia
Sa, Rina
Liang, Houjie
author_facet Ou, Juanjuan
Luan, Wei
Deng, Jia
Sa, Rina
Liang, Houjie
author_sort Ou, Juanjuan
collection PubMed
description BACKGROUND: Tumor cells acquire the capacity of resistance to chemotherapy or radiotherapy via cell–matrix and cell–cell crosstalk. Integrins are the most important cell adhesion molecules, in which αV integrin mainly mediating the tight contact between tumor cells. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the role of αV integrin in multi-cellular radioresistance (MCR) of human nasopharyngeal carcinoma (NPC), we performed immunohistochemistry and Western blotting to find that the expression of αV integrin in the tumor tissue of radioresistant patients is much higher than that in radiosensitive patients. In vitro, we cultured human NPC cell line CNE-2 cells as multi-cellular spheroids (MCSs) or as monolayer cells (MCs), and found that the expression of αV integrin in MCSs is significantly higher than that in MCs. MTT, flow cytometry and clonogenic suvival assays showed that MCSs are less sensitive to X-ray irradiation than MCs while blocking of αV integrin in MCSs dramatically reversed their radioresistance. Furthermore, as detected by Western blotting, MCSs displayed sustained activation of the stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) pathway in presence of irradiation. Blocking of αV integrin in MCSs decreased the expression of phosphorylated JNK. Additionally, blocking of SAPK/JNK signaling pathway synergistically induced apoptosis of MCSs exposed to irradiation by increasing the expression of cleaved caspase-3. In vivo, we found that irradiation combined with αV integrin blocking treatment significantly enhanced the radiosensitivity of NPC xenografts. CONCLUSIONS: Our results indicate a novel role of αV integrin in multi-cellular radioresistance of NPCs.
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spelling pubmed-33748392012-06-20 αV Integrin Induces Multicellular Radioresistance in Human Nasopharyngeal Carcinoma via Activating SAPK/JNK Pathway Ou, Juanjuan Luan, Wei Deng, Jia Sa, Rina Liang, Houjie PLoS One Research Article BACKGROUND: Tumor cells acquire the capacity of resistance to chemotherapy or radiotherapy via cell–matrix and cell–cell crosstalk. Integrins are the most important cell adhesion molecules, in which αV integrin mainly mediating the tight contact between tumor cells. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the role of αV integrin in multi-cellular radioresistance (MCR) of human nasopharyngeal carcinoma (NPC), we performed immunohistochemistry and Western blotting to find that the expression of αV integrin in the tumor tissue of radioresistant patients is much higher than that in radiosensitive patients. In vitro, we cultured human NPC cell line CNE-2 cells as multi-cellular spheroids (MCSs) or as monolayer cells (MCs), and found that the expression of αV integrin in MCSs is significantly higher than that in MCs. MTT, flow cytometry and clonogenic suvival assays showed that MCSs are less sensitive to X-ray irradiation than MCs while blocking of αV integrin in MCSs dramatically reversed their radioresistance. Furthermore, as detected by Western blotting, MCSs displayed sustained activation of the stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) pathway in presence of irradiation. Blocking of αV integrin in MCSs decreased the expression of phosphorylated JNK. Additionally, blocking of SAPK/JNK signaling pathway synergistically induced apoptosis of MCSs exposed to irradiation by increasing the expression of cleaved caspase-3. In vivo, we found that irradiation combined with αV integrin blocking treatment significantly enhanced the radiosensitivity of NPC xenografts. CONCLUSIONS: Our results indicate a novel role of αV integrin in multi-cellular radioresistance of NPCs. Public Library of Science 2012-06-13 /pmc/articles/PMC3374839/ /pubmed/22719931 http://dx.doi.org/10.1371/journal.pone.0038737 Text en Ou et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ou, Juanjuan
Luan, Wei
Deng, Jia
Sa, Rina
Liang, Houjie
αV Integrin Induces Multicellular Radioresistance in Human Nasopharyngeal Carcinoma via Activating SAPK/JNK Pathway
title αV Integrin Induces Multicellular Radioresistance in Human Nasopharyngeal Carcinoma via Activating SAPK/JNK Pathway
title_full αV Integrin Induces Multicellular Radioresistance in Human Nasopharyngeal Carcinoma via Activating SAPK/JNK Pathway
title_fullStr αV Integrin Induces Multicellular Radioresistance in Human Nasopharyngeal Carcinoma via Activating SAPK/JNK Pathway
title_full_unstemmed αV Integrin Induces Multicellular Radioresistance in Human Nasopharyngeal Carcinoma via Activating SAPK/JNK Pathway
title_short αV Integrin Induces Multicellular Radioresistance in Human Nasopharyngeal Carcinoma via Activating SAPK/JNK Pathway
title_sort αv integrin induces multicellular radioresistance in human nasopharyngeal carcinoma via activating sapk/jnk pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374839/
https://www.ncbi.nlm.nih.gov/pubmed/22719931
http://dx.doi.org/10.1371/journal.pone.0038737
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