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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.
Afiliação
  • Fujita M; Department of Molecular Patho-Physiology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
  • Yamamoto T; Department of Neurosurgery, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
  • Iyoda T; Department of Pharmacy, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, 1-1-1 Daigaku-Doori, Sanyo-Onoda, Yamaguchi 756-0884, Japan.
  • Fujisawa T; Department of Molecular Patho-Physiology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
  • Nagai R; Department of Molecular Patho-Physiology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
  • Kudo C; Department of Molecular Patho-Physiology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
  • Sasada M; Department of Molecular Patho-Physiology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
  • Kodama H; Faculty of Science and Engineering, Saga University, 1 Honjo-machi, Saga-city, Saga 840-8502, Japan.
  • Fukai F; Department of Molecular Patho-Physiology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. fukai@rs.noda.tus.ac.jp.
Int J Mol Sci ; 20(13)2019 Jun 28.
Article em En | MEDLINE | ID: mdl-31261783
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 ß1-integrins. Our recent study demonstrated that potentiated activation of integrin α5ß1 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-receptorß, 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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Fator de Crescimento Derivado de Plaquetas / Glioblastoma / Tenascina / Comunicação Autócrina / Proliferação de Células Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Int J Mol Sci Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Fator de Crescimento Derivado de Plaquetas / Glioblastoma / Tenascina / Comunicação Autócrina / Proliferação de Células Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Int J Mol Sci Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Japão