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HYBID derived from tumor cells and tumor-associated macrophages contribute to the glioblastoma growth.
Tsuji, Shohei; Nakamura, Shinsuke; Yamada, Tetsuya; de Vega, Susana; Okada, Yasunori; Inoue, Shintaro; Shimazawa, Masamitsu; Hara, Hideaki.
Afiliación
  • Tsuji S; Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
  • Nakamura S; Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
  • Yamada T; Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan; Department of Neurosurgery, Gifu University School of Medicine, Gifu, Japan.
  • de Vega S; Department of Pathophysiology for Locomotive and Neoplastic Diseases, Juntendo University Graduate School of Medicine, Tokyo, Japan.
  • Okada Y; Department of Pathophysiology for Locomotive and Neoplastic Diseases, Juntendo University Graduate School of Medicine, Tokyo, Japan.
  • Inoue S; Cosmetic Health Science, Gifu Pharmaceutical University, Gifu, Japan.
  • Shimazawa M; Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
  • Hara H; Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan. Electronic address: hidehara@gifu-pu.ac.jp.
Brain Res ; 1764: 147490, 2021 08 01.
Article en En | MEDLINE | ID: mdl-33887254
Glioblastoma is the most malignant tumor of the brain associated with poor prognosis and outcome, and hence there is an urgent need to develop novel treatments for glioblastoma. In this study, we focused on hyaluronan binding protein (HYBID, as known as CEMIP/KIAA1199), a protein involved in hyaluronan depolymerization in chondrocytes and synoviocytes. We previously reported that Hybid-deficient (KO) mice show accumulation of hyaluronan in the brain, and memory impairment. To elucidate the role of HYBID in glioblastoma pathogenesis, we knocked down HYBID in human glioblastoma cells using siRNAs and developed a murine orthotopic xenograft model in the Hybid KO mice. Downregulation of HYBID in glioblastoma cells resulted in inhibition of cell proliferation and migration, and increased cell death. The growth of glioblastoma cells implanted in the mouse brain was suppressed in Hybid KO mice compared to that in the wild-type mice. Interestingly, infiltration of macrophages in the glioblastoma tissue was decreased in Hybid KO mice. Using intraperitoneal macrophages derived from Hybid KO mice and glioma cell supernatants, we examined the role of HYBID in macrophages in the tumor environment. We showed that HYBID contributes to macrophage migration and the release of pro-tumor factors. Moreover, we revealed that HYBID can be a poor prognostic factor in glioma patients by bioinformatics approaches. Our study provides data to support that HYBID expressed by both glioblastoma cells and tumor-associated macrophages may contribute to glioblastoma progression and suggests that HYBID may be a potential target for therapy that focuses on the tumor microenvironment of glioblastoma.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 6_ODS3_enfermedades_notrasmisibles Problema de salud: 6_brain_nervous_system_cancer Asunto principal: Neoplasias Encefálicas / Glioblastoma / Hialuronoglucosaminidasa / Macrófagos / Neoplasias Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Humans / Male Idioma: En Revista: Brain Res Año: 2021 Tipo del documento: Article País de afiliación: Japón

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 6_ODS3_enfermedades_notrasmisibles Problema de salud: 6_brain_nervous_system_cancer Asunto principal: Neoplasias Encefálicas / Glioblastoma / Hialuronoglucosaminidasa / Macrófagos / Neoplasias Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Humans / Male Idioma: En Revista: Brain Res Año: 2021 Tipo del documento: Article País de afiliación: Japón
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