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Autocrine Production of PDGF Stimulated by the Tenascin-C-Derived Peptide TNIIIA2 Induces Hyper-Proliferation in Glioblastoma Cells

Expression level of tenascin-C is closely correlated to poor prognosis in glioblastoma patients, while the substantial role of tenascin-C responsible for aggressive progression in glioblastoma cells has not been clarified. We previously found that peptide TNIIIA2, which is derived from the tumor-ass...

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Autores principales: Fujita, Motomichi, Yamamoto, Tetsuya, Iyoda, Takuya, Fujisawa, Tatsuya, Nagai, Reo, Kudo, Chikako, Sasada, Manabu, Kodama, Hiroaki, Fukai, Fumio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651645/
https://www.ncbi.nlm.nih.gov/pubmed/31261783
http://dx.doi.org/10.3390/ijms20133183
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author Fujita, Motomichi
Yamamoto, Tetsuya
Iyoda, Takuya
Fujisawa, Tatsuya
Nagai, Reo
Kudo, Chikako
Sasada, Manabu
Kodama, Hiroaki
Fukai, Fumio
author_facet Fujita, Motomichi
Yamamoto, Tetsuya
Iyoda, Takuya
Fujisawa, Tatsuya
Nagai, Reo
Kudo, Chikako
Sasada, Manabu
Kodama, Hiroaki
Fukai, Fumio
author_sort Fujita, Motomichi
collection PubMed
description Expression level of tenascin-C is closely correlated to poor prognosis in glioblastoma patients, while the substantial role of tenascin-C responsible for aggressive progression in glioblastoma cells has not been clarified. We previously found that peptide TNIIIA2, which is derived from the tumor-associated tenascin-C variants, has the ability to promote cell adhesion by activating β1-integrins. Our recent study demonstrated that potentiated activation of integrin α5β1 by TNIIIA2 causes not only a dysregulated proliferation in a platelet-derived growth factor (PDGF)-dependent manner, but also disseminative migration in glioblastoma cells. Here, we show that TNIIIA2 enhances the proliferation in glioblastoma cells expressing PDGF-receptorβ, even without exogenous PDGF. Mechanistically, TNIIIA2 induced upregulated expression of PDGF, which in turn stimulated the expression of tenascin-C, a parental molecule of TNIIIA2. Moreover, in glioblastoma cells and rat brain-derived fibroblasts, tenascin-C upregulated matrix metalloproteinase-2, which has the potential to release TNIIIA2 from tenascin-C. Thus, it was shown that autocrine production of PDGF triggered by TNIIIA2 functions to continuously generate a functional amount of PDGF through a positive spiral loop, which might contribute to hyper-proliferation in glioblastoma cells. TNIIIA2 also enhanced in vitro disseminative migration of glioblastoma cells via the PKCα signaling. Collectively, the tenascin-C/TNIIIA2 could be a potential therapeutic target for glioblastoma.
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spelling pubmed-66516452019-08-08 Autocrine Production of PDGF Stimulated by the Tenascin-C-Derived Peptide TNIIIA2 Induces Hyper-Proliferation in Glioblastoma Cells Fujita, Motomichi Yamamoto, Tetsuya Iyoda, Takuya Fujisawa, Tatsuya Nagai, Reo Kudo, Chikako Sasada, Manabu Kodama, Hiroaki Fukai, Fumio Int J Mol Sci Article Expression level of tenascin-C is closely correlated to poor prognosis in glioblastoma patients, while the substantial role of tenascin-C responsible for aggressive progression in glioblastoma cells has not been clarified. We previously found that peptide TNIIIA2, which is derived from the tumor-associated tenascin-C variants, has the ability to promote cell adhesion by activating β1-integrins. Our recent study demonstrated that potentiated activation of integrin α5β1 by TNIIIA2 causes not only a dysregulated proliferation in a platelet-derived growth factor (PDGF)-dependent manner, but also disseminative migration in glioblastoma cells. Here, we show that TNIIIA2 enhances the proliferation in glioblastoma cells expressing PDGF-receptorβ, even without exogenous PDGF. Mechanistically, TNIIIA2 induced upregulated expression of PDGF, which in turn stimulated the expression of tenascin-C, a parental molecule of TNIIIA2. Moreover, in glioblastoma cells and rat brain-derived fibroblasts, tenascin-C upregulated matrix metalloproteinase-2, which has the potential to release TNIIIA2 from tenascin-C. Thus, it was shown that autocrine production of PDGF triggered by TNIIIA2 functions to continuously generate a functional amount of PDGF through a positive spiral loop, which might contribute to hyper-proliferation in glioblastoma cells. TNIIIA2 also enhanced in vitro disseminative migration of glioblastoma cells via the PKCα signaling. Collectively, the tenascin-C/TNIIIA2 could be a potential therapeutic target for glioblastoma. MDPI 2019-06-28 /pmc/articles/PMC6651645/ /pubmed/31261783 http://dx.doi.org/10.3390/ijms20133183 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fujita, Motomichi
Yamamoto, Tetsuya
Iyoda, Takuya
Fujisawa, Tatsuya
Nagai, Reo
Kudo, Chikako
Sasada, Manabu
Kodama, Hiroaki
Fukai, Fumio
Autocrine Production of PDGF Stimulated by the Tenascin-C-Derived Peptide TNIIIA2 Induces Hyper-Proliferation in Glioblastoma Cells
title Autocrine Production of PDGF Stimulated by the Tenascin-C-Derived Peptide TNIIIA2 Induces Hyper-Proliferation in Glioblastoma Cells
title_full Autocrine Production of PDGF Stimulated by the Tenascin-C-Derived Peptide TNIIIA2 Induces Hyper-Proliferation in Glioblastoma Cells
title_fullStr Autocrine Production of PDGF Stimulated by the Tenascin-C-Derived Peptide TNIIIA2 Induces Hyper-Proliferation in Glioblastoma Cells
title_full_unstemmed Autocrine Production of PDGF Stimulated by the Tenascin-C-Derived Peptide TNIIIA2 Induces Hyper-Proliferation in Glioblastoma Cells
title_short Autocrine Production of PDGF Stimulated by the Tenascin-C-Derived Peptide TNIIIA2 Induces Hyper-Proliferation in Glioblastoma Cells
title_sort autocrine production of pdgf stimulated by the tenascin-c-derived peptide tniiia2 induces hyper-proliferation in glioblastoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651645/
https://www.ncbi.nlm.nih.gov/pubmed/31261783
http://dx.doi.org/10.3390/ijms20133183
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