WEKO3
アイテム
Endothelial-Mesenchymal Transition in Tumor Microenvironment Promotes Neuroendocrine Differentiation of Prostate Cancer
http://hdl.handle.net/10076/0002001684
http://hdl.handle.net/10076/0002001684af41bb29-bab4-4626-907b-d5475fd485aa
| 名前 / ファイル | ライセンス | アクション |
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2025DM1204.pdf (4.27 MB)
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2025DM1204-supplement.docx (1.3 MB)
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| アイテムタイプ | 学位論文 / Thesis or Dissertation(1) | |||||||||||
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| 公開日 | 2026-01-22 | |||||||||||
| タイトル | ||||||||||||
| タイトル | Endothelial-Mesenchymal Transition in Tumor Microenvironment Promotes Neuroendocrine Differentiation of Prostate Cancer | |||||||||||
| 言語 | en | |||||||||||
| 言語 | ||||||||||||
| 言語 | eng | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | androgen deprivation therapy | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | endothelial-mesenchymal transition | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | granulocyte-macrophage colony-stimulating factor | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | neuroendocrine differentiation | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | prostate cancer | |||||||||||
| 資源タイプ | ||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||||
| 資源タイプ | doctoral thesis | |||||||||||
| アクセス権 | ||||||||||||
| アクセス権 | open access | |||||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||||
| 著者 |
景山, 拓海
× 景山, 拓海
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| 抄録 | ||||||||||||
| 内容記述タイプ | Abstract | |||||||||||
| 内容記述 | Neuroendocrine prostate cancer (NEPC) is a highly aggressive and treatment-resistant subtype of castration-resistant prostate cancer (CRPC) that often emerges during progression under androgen-receptor (AR) pathway inhibition. While lineage plasticity in cancer cells has been recognized as a key mechanism of resistance, the role of the tumor microenvironment in driving this transition remains unclear. Among its cellular components, vascular endothelial cells can undergo endothelial-mesenchymal transition (EndoMT), a phenotypic shift associated with tumor progression and fibrosis. Here, we investigated whether EndoMT contributes to NEPC development. Human umbilical vein endothelial cells (HUVEC) were induced to undergo EndoMT using IL-1β and TGF-β2, and are hereafter referred to as EndoMTed HUVEC. EndoMTed HUVEC promoted neuroendocrine features and functional changes in LNCaP cells. Transcriptome analysis revealed marked upregulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) in EndoMTed HUVEC. Neutralization of GM-CSF signaling using mavrilimumab, a monoclonal antibody targeting the GM-CSF receptor alpha (CSF2RA), and siRNA-mediated CSF2RA knockdown both suppressed the neuroendocrine phenotype and STAT3 signaling of LNCaP cells. Conversely, GM-CSF stimulation alone reproduced these changes. Enzalutamide-treated LNCaP cells secreted IL-1β and TGF-β2, which in turn triggered EndoMT, suggesting a reciprocal loop. These findings indicate that anti-androgen therapy may inadvertently promote NEPC through a paracrine loop involving tumor-derived cytokines and endothelial GM-CSF secretion, highlighting EndoMT as a microenvironmental driver of treatment resistance. | |||||||||||
| 言語 | en | |||||||||||
| 内容記述 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | 本文 / Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu, Japan | |||||||||||
| 内容記述 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | 11p | |||||||||||
| 書誌情報 |
発行日 2025-12-17 |
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| DOI | ||||||||||||
| 識別子タイプ | DOI | |||||||||||
| 関連識別子 | 10.1111/cas.70144 | |||||||||||
| フォーマット | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | application/pdf | |||||||||||
| 出版者 | ||||||||||||
| 出版者 | 三重大学 | |||||||||||
| 出版者（ヨミ） | ||||||||||||
| 値 | ミエダイガク | |||||||||||
| 学位名 | ||||||||||||
| 学位名 | 博士(医学) | |||||||||||
| 学位授与機関 | ||||||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||||||
| 学位授与機関識別子 | 14101 | |||||||||||
| 学位授与機関名 | 三重大学 | |||||||||||
| 学位授与年月日 | ||||||||||||
| 学位授与年月日 | 2025-12-17 | |||||||||||
| 学位授与番号 | ||||||||||||
| 学位授与番号 | 甲医学第2352号 | |||||||||||
| 資源タイプ（三重大） | ||||||||||||
| 値 | Doctoral Dissertation / 博士論文 | |||||||||||
