Targeting PTPRZ inhibits stem cell-like properties and tumorigenicity in glioblastoma cells

Abstract The R5 subfamily of receptor-type protein tyrosine phosphatases (RPTPs) comprises PTPRZ and PTPRG. A recent study on primary human glioblastomas suggested a close association between PTPRZ1 (human PTPRZ) expression and cancer stemness. However, the functional roles of PTPRZ activity in glio...

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Autores principales:	Akihiro Fujikawa, Hajime Sugawara, Taisaku Tanaka, Masahito Matsumoto, Kazuya Kuboyama, Ryoko Suzuki, Naomi Tanga, Atsuto Ogata, Makoto Masumura, Masaharu Noda
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6fee56b055c14364a010dc2e318654be
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spelling	oai:doaj.org-article:6fee56b055c14364a010dc2e318654be2021-12-02T16:07:04ZTargeting PTPRZ inhibits stem cell-like properties and tumorigenicity in glioblastoma cells10.1038/s41598-017-05931-82045-2322https://doaj.org/article/6fee56b055c14364a010dc2e318654be2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05931-8https://doaj.org/toc/2045-2322Abstract The R5 subfamily of receptor-type protein tyrosine phosphatases (RPTPs) comprises PTPRZ and PTPRG. A recent study on primary human glioblastomas suggested a close association between PTPRZ1 (human PTPRZ) expression and cancer stemness. However, the functional roles of PTPRZ activity in glioma stem cells have remained unclear. In the present study, we found that sphere-forming cells from the rat C6 and human U251 glioblastoma cell lines showed high expression levels of PTPRZ-B, the short receptor isoform of PTPRZ. Stable PTPRZ knockdown altered the expression levels of stem cell transcription factors such as SOX2, OLIG2, and POU3F2 and decreased the sphere-forming abilities of these cells. Suppressive effects on the cancer stem-like properties of the cells were also observed following the knockdown of PTPRG. Here, we identified NAZ2329, a cell-permeable small molecule that allosterically inhibits both PTPRZ and PTPRG. NAZ2329 reduced the expression of SOX2 in C6 and U251 cells and abrogated the sphere-forming abilities of these cells. Tumor growth in the C6 xenograft mouse model was significantly slower with the co-treatment of NAZ2329 with temozolomide, an alkylating agent, than with the individual treatments. These results indicate that pharmacological inhibition of R5 RPTPs is a promising strategy for the treatment of malignant gliomas.Akihiro FujikawaHajime SugawaraTaisaku TanakaMasahito MatsumotoKazuya KuboyamaRyoko SuzukiNaomi TangaAtsuto OgataMakoto MasumuraMasaharu NodaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-17 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Akihiro Fujikawa Hajime Sugawara Taisaku Tanaka Masahito Matsumoto Kazuya Kuboyama Ryoko Suzuki Naomi Tanga Atsuto Ogata Makoto Masumura Masaharu Noda Targeting PTPRZ inhibits stem cell-like properties and tumorigenicity in glioblastoma cells
description	Abstract The R5 subfamily of receptor-type protein tyrosine phosphatases (RPTPs) comprises PTPRZ and PTPRG. A recent study on primary human glioblastomas suggested a close association between PTPRZ1 (human PTPRZ) expression and cancer stemness. However, the functional roles of PTPRZ activity in glioma stem cells have remained unclear. In the present study, we found that sphere-forming cells from the rat C6 and human U251 glioblastoma cell lines showed high expression levels of PTPRZ-B, the short receptor isoform of PTPRZ. Stable PTPRZ knockdown altered the expression levels of stem cell transcription factors such as SOX2, OLIG2, and POU3F2 and decreased the sphere-forming abilities of these cells. Suppressive effects on the cancer stem-like properties of the cells were also observed following the knockdown of PTPRG. Here, we identified NAZ2329, a cell-permeable small molecule that allosterically inhibits both PTPRZ and PTPRG. NAZ2329 reduced the expression of SOX2 in C6 and U251 cells and abrogated the sphere-forming abilities of these cells. Tumor growth in the C6 xenograft mouse model was significantly slower with the co-treatment of NAZ2329 with temozolomide, an alkylating agent, than with the individual treatments. These results indicate that pharmacological inhibition of R5 RPTPs is a promising strategy for the treatment of malignant gliomas.
format	article
author	Akihiro Fujikawa Hajime Sugawara Taisaku Tanaka Masahito Matsumoto Kazuya Kuboyama Ryoko Suzuki Naomi Tanga Atsuto Ogata Makoto Masumura Masaharu Noda
author_facet	Akihiro Fujikawa Hajime Sugawara Taisaku Tanaka Masahito Matsumoto Kazuya Kuboyama Ryoko Suzuki Naomi Tanga Atsuto Ogata Makoto Masumura Masaharu Noda
author_sort	Akihiro Fujikawa
title	Targeting PTPRZ inhibits stem cell-like properties and tumorigenicity in glioblastoma cells
title_short	Targeting PTPRZ inhibits stem cell-like properties and tumorigenicity in glioblastoma cells
title_full	Targeting PTPRZ inhibits stem cell-like properties and tumorigenicity in glioblastoma cells
title_fullStr	Targeting PTPRZ inhibits stem cell-like properties and tumorigenicity in glioblastoma cells
title_full_unstemmed	Targeting PTPRZ inhibits stem cell-like properties and tumorigenicity in glioblastoma cells
title_sort	targeting ptprz inhibits stem cell-like properties and tumorigenicity in glioblastoma cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6fee56b055c14364a010dc2e318654be
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Targeting PTPRZ inhibits stem cell-like properties and tumorigenicity in glioblastoma cells

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