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Overexpression of Notch3 is associated with metastasis and poor prognosis in osteosarcoma patients

BACKGROUND: Notch signaling abnormalities are associated with the development of various tumors, including hematopoietic and epithelium-derived tumors. However, the role of Notch signaling in tumors originating from mesenchymal cells is unclear. The effect of Notch3 expression on the prognosis of os...

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Autores principales: Tang, Xue-Feng, Cao, Ya, Peng, Dong-Bin, Zhao, Guo-Sheng, Zeng, Ying, Gao, Zi-Ran, Lv, Yang-Fan, Guo, Qiao-Nan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329347/
https://www.ncbi.nlm.nih.gov/pubmed/30662285
http://dx.doi.org/10.2147/CMAR.S185495
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author Tang, Xue-Feng
Cao, Ya
Peng, Dong-Bin
Zhao, Guo-Sheng
Zeng, Ying
Gao, Zi-Ran
Lv, Yang-Fan
Guo, Qiao-Nan
author_facet Tang, Xue-Feng
Cao, Ya
Peng, Dong-Bin
Zhao, Guo-Sheng
Zeng, Ying
Gao, Zi-Ran
Lv, Yang-Fan
Guo, Qiao-Nan
author_sort Tang, Xue-Feng
collection PubMed
description BACKGROUND: Notch signaling abnormalities are associated with the development of various tumors, including hematopoietic and epithelium-derived tumors. However, the role of Notch signaling in tumors originating from mesenchymal cells is unclear. The effect of Notch3 expression on the prognosis of osteosarcoma and its role and mechanism in osteosarcoma cells have never been reported. MATERIALS AND METHODS: In this study, we performed a clinicopathological analysis of 70 cases of osteosarcoma, with primary focus on survival. Osteosarcoma cell lines MTH and U2OS were used. After knockdown of Notch3 by lentiviral transfection and siRNA, the cell cycle, cell viability, and wound healing capacity were assessed. Subsequently, the Transwell assay was performed, and the expression levels of hairy and enhancer of split-1 (Hes1) and matrix metalloproteinase 7 (MMP7) were detected by RT-PCR and Western blot assay. The expression of MMP7 was also detected after knockdown of Hes1. Animal experiments were performed by injecting the cell lines MTH of Notch3 knockdown into mice tail veins and comparing the development of lung metastasis with the control group. RESULTS: Comparison of survival curves showed that Notch3 expression significantly impacts patient survival. Additionally, multivariate analysis revealed that Notch3 is an independent prognostic factor for osteosarcoma. In in vivo experiments, osteosarcoma-associated pulmonary metastasis in nude mice was reduced after Notch3 silencing. The expression of downstream effector molecule, Hes1, and that of the invasion and metastasis-associated proteolytic enzyme, MMP7, were reduced, and MMP7 was further decreased by Hes1 knockdown in in vitro experiments. CONCLUSION: Notch3 is a prognostic factor for osteosarcoma and might regulate its invasion and metastasis through the downstream target gene Hes1 and effector MMP7.
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spelling pubmed-63293472019-01-18 Overexpression of Notch3 is associated with metastasis and poor prognosis in osteosarcoma patients Tang, Xue-Feng Cao, Ya Peng, Dong-Bin Zhao, Guo-Sheng Zeng, Ying Gao, Zi-Ran Lv, Yang-Fan Guo, Qiao-Nan Cancer Manag Res Original Research BACKGROUND: Notch signaling abnormalities are associated with the development of various tumors, including hematopoietic and epithelium-derived tumors. However, the role of Notch signaling in tumors originating from mesenchymal cells is unclear. The effect of Notch3 expression on the prognosis of osteosarcoma and its role and mechanism in osteosarcoma cells have never been reported. MATERIALS AND METHODS: In this study, we performed a clinicopathological analysis of 70 cases of osteosarcoma, with primary focus on survival. Osteosarcoma cell lines MTH and U2OS were used. After knockdown of Notch3 by lentiviral transfection and siRNA, the cell cycle, cell viability, and wound healing capacity were assessed. Subsequently, the Transwell assay was performed, and the expression levels of hairy and enhancer of split-1 (Hes1) and matrix metalloproteinase 7 (MMP7) were detected by RT-PCR and Western blot assay. The expression of MMP7 was also detected after knockdown of Hes1. Animal experiments were performed by injecting the cell lines MTH of Notch3 knockdown into mice tail veins and comparing the development of lung metastasis with the control group. RESULTS: Comparison of survival curves showed that Notch3 expression significantly impacts patient survival. Additionally, multivariate analysis revealed that Notch3 is an independent prognostic factor for osteosarcoma. In in vivo experiments, osteosarcoma-associated pulmonary metastasis in nude mice was reduced after Notch3 silencing. The expression of downstream effector molecule, Hes1, and that of the invasion and metastasis-associated proteolytic enzyme, MMP7, were reduced, and MMP7 was further decreased by Hes1 knockdown in in vitro experiments. CONCLUSION: Notch3 is a prognostic factor for osteosarcoma and might regulate its invasion and metastasis through the downstream target gene Hes1 and effector MMP7. Dove Medical Press 2019-01-08 /pmc/articles/PMC6329347/ /pubmed/30662285 http://dx.doi.org/10.2147/CMAR.S185495 Text en © 2019 Tang et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Tang, Xue-Feng
Cao, Ya
Peng, Dong-Bin
Zhao, Guo-Sheng
Zeng, Ying
Gao, Zi-Ran
Lv, Yang-Fan
Guo, Qiao-Nan
Overexpression of Notch3 is associated with metastasis and poor prognosis in osteosarcoma patients
title Overexpression of Notch3 is associated with metastasis and poor prognosis in osteosarcoma patients
title_full Overexpression of Notch3 is associated with metastasis and poor prognosis in osteosarcoma patients
title_fullStr Overexpression of Notch3 is associated with metastasis and poor prognosis in osteosarcoma patients
title_full_unstemmed Overexpression of Notch3 is associated with metastasis and poor prognosis in osteosarcoma patients
title_short Overexpression of Notch3 is associated with metastasis and poor prognosis in osteosarcoma patients
title_sort overexpression of notch3 is associated with metastasis and poor prognosis in osteosarcoma patients
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329347/
https://www.ncbi.nlm.nih.gov/pubmed/30662285
http://dx.doi.org/10.2147/CMAR.S185495
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