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Novel cancer stem cell marker MVP enhances temozolomide-resistance in glioblastoma

The resistance of highly aggressive glioblastoma multiforme (GBM) to chemotherapy is a major clinical problem resulting in a poor prognosis. GBM contains a rare population of self-renewing cancer stem cells (CSCs) that proliferate, spurring the growth of new tumors, and evade chemotherapy. In cancer...

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Autores principales: Noh, Kum Hee, Lee, Song-Hee, Lee, Haeri, Jeong, Ae Jin, Kim, Kyu Oh, Shin, Hyun Mu, Kim, Hang-Rae, Park, Myung-Jin, Park, Jong Bae, Lee, Jiyoung, Ye, Sang-Kyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577150/
https://www.ncbi.nlm.nih.gov/pubmed/34742152
http://dx.doi.org/10.1016/j.tranon.2021.101255
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author Noh, Kum Hee
Lee, Song-Hee
Lee, Haeri
Jeong, Ae Jin
Kim, Kyu Oh
Shin, Hyun Mu
Kim, Hang-Rae
Park, Myung-Jin
Park, Jong Bae
Lee, Jiyoung
Ye, Sang-Kyu
author_facet Noh, Kum Hee
Lee, Song-Hee
Lee, Haeri
Jeong, Ae Jin
Kim, Kyu Oh
Shin, Hyun Mu
Kim, Hang-Rae
Park, Myung-Jin
Park, Jong Bae
Lee, Jiyoung
Ye, Sang-Kyu
author_sort Noh, Kum Hee
collection PubMed
description The resistance of highly aggressive glioblastoma multiforme (GBM) to chemotherapy is a major clinical problem resulting in a poor prognosis. GBM contains a rare population of self-renewing cancer stem cells (CSCs) that proliferate, spurring the growth of new tumors, and evade chemotherapy. In cancer, major vault protein (MVP) is thought to contribute to drug resistance. However, the role of MVP as CSCs marker remains unknown and whether MVP could sensitize GBM cells to Temozolomide (TMZ) also is unclear. We found that sensitivity to TMZ was suppressed by significantly increasing the MVP expression in GBM cells with TMZ resistance. Also, MVP was associated with the expression of other multidrug-resistant proteins in tumorsphere of TMZ-resistant GBM cell, and was highly co-expressed with CSC markers in tumorsphere culture. On the other hands, knockdown of MVP resulted in reduced sphere formation and invasive capacity. Moreover, high expression of MVP was associated with tumor malignancy and survival rate in glioblastoma patients. Our study describes that MVP is a potentially novel maker for glioblastoma stem cells and may be useful as a target for preventing TMZ resistance in GBM patients.
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spelling pubmed-85771502021-11-19 Novel cancer stem cell marker MVP enhances temozolomide-resistance in glioblastoma Noh, Kum Hee Lee, Song-Hee Lee, Haeri Jeong, Ae Jin Kim, Kyu Oh Shin, Hyun Mu Kim, Hang-Rae Park, Myung-Jin Park, Jong Bae Lee, Jiyoung Ye, Sang-Kyu Transl Oncol Original Research The resistance of highly aggressive glioblastoma multiforme (GBM) to chemotherapy is a major clinical problem resulting in a poor prognosis. GBM contains a rare population of self-renewing cancer stem cells (CSCs) that proliferate, spurring the growth of new tumors, and evade chemotherapy. In cancer, major vault protein (MVP) is thought to contribute to drug resistance. However, the role of MVP as CSCs marker remains unknown and whether MVP could sensitize GBM cells to Temozolomide (TMZ) also is unclear. We found that sensitivity to TMZ was suppressed by significantly increasing the MVP expression in GBM cells with TMZ resistance. Also, MVP was associated with the expression of other multidrug-resistant proteins in tumorsphere of TMZ-resistant GBM cell, and was highly co-expressed with CSC markers in tumorsphere culture. On the other hands, knockdown of MVP resulted in reduced sphere formation and invasive capacity. Moreover, high expression of MVP was associated with tumor malignancy and survival rate in glioblastoma patients. Our study describes that MVP is a potentially novel maker for glioblastoma stem cells and may be useful as a target for preventing TMZ resistance in GBM patients. Neoplasia Press 2021-11-02 /pmc/articles/PMC8577150/ /pubmed/34742152 http://dx.doi.org/10.1016/j.tranon.2021.101255 Text en © 2021 The Authors. Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Noh, Kum Hee
Lee, Song-Hee
Lee, Haeri
Jeong, Ae Jin
Kim, Kyu Oh
Shin, Hyun Mu
Kim, Hang-Rae
Park, Myung-Jin
Park, Jong Bae
Lee, Jiyoung
Ye, Sang-Kyu
Novel cancer stem cell marker MVP enhances temozolomide-resistance in glioblastoma
title Novel cancer stem cell marker MVP enhances temozolomide-resistance in glioblastoma
title_full Novel cancer stem cell marker MVP enhances temozolomide-resistance in glioblastoma
title_fullStr Novel cancer stem cell marker MVP enhances temozolomide-resistance in glioblastoma
title_full_unstemmed Novel cancer stem cell marker MVP enhances temozolomide-resistance in glioblastoma
title_short Novel cancer stem cell marker MVP enhances temozolomide-resistance in glioblastoma
title_sort novel cancer stem cell marker mvp enhances temozolomide-resistance in glioblastoma
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577150/
https://www.ncbi.nlm.nih.gov/pubmed/34742152
http://dx.doi.org/10.1016/j.tranon.2021.101255
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