Scholarlink

<p>The blood–brain barrier (BBB) is a highly selective barrier that strictly controls the passage of substances and cells into the brain, protecting it from potential harm while preserving homeostasis. It is composed of specialised endothelial cells (ECs), along with surrounding cells, such as pericytes and astrocytes. In glioblastoma (GBM), the most prevalent primary malignant brain tumour in adults, the BBB is heterogeneously dysfunctional. In the tumour microenvironment, regions enriched with glioblastoma stem cells (GSCs) are protected by an intact BBB. However, the influence of GSCs on BBB function remains largely unexplored. In this study, the impact of patient-derived GSC (PD GSC) secretomes on human brain capillary ECs has been investigated in vitro. Results showed that secretomes decrease the BBB permeability, leading to an increase of transendothelial electrical resistance and of tight junction protein claudin-5 (CLDN5) levels. Moreover, the receptor for advanced glycation endproducts (RAGE), which is involved in cancer and chemotherapy resistance, modulates CLDN5 expression by activating the pERK/ERK signaling pathway and influences junctional organization. These findings suggest a functional pathway through which PD GSC secretomes can modulate BBB permeability, potentially impacting therapeutic efficacy.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Modulation of the blood–brain barrier permeability by patient-derived glioblastoma stem cell secretome

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月27日

查看全文
  • Francesco Saverio Sica,
  • Michela Patrucco,
  • Martina Giambra,
  • Martina Ghizzi,
  • Silvia Sesana,
  • Barbara Vergani,
  • Biagio Eugenio Leone,
  • Andrea Di Cristofori,
  • Carlo Giorgio Giussani,
  • Gabriella Nicolini,
  • Angela Bentivegna,
  • Francesca Re

摘要

The blood–brain barrier (BBB) is a highly selective barrier that strictly controls the passage of substances and cells into the brain, protecting it from potential harm while preserving homeostasis. It is composed of specialised endothelial cells (ECs), along with surrounding cells, such as pericytes and astrocytes. In glioblastoma (GBM), the most prevalent primary malignant brain tumour in adults, the BBB is heterogeneously dysfunctional. In the tumour microenvironment, regions enriched with glioblastoma stem cells (GSCs) are protected by an intact BBB. However, the influence of GSCs on BBB function remains largely unexplored. In this study, the impact of patient-derived GSC (PD GSC) secretomes on human brain capillary ECs has been investigated in vitro. Results showed that secretomes decrease the BBB permeability, leading to an increase of transendothelial electrical resistance and of tight junction protein claudin-5 (CLDN5) levels. Moreover, the receptor for advanced glycation endproducts (RAGE), which is involved in cancer and chemotherapy resistance, modulates CLDN5 expression by activating the pERK/ERK signaling pathway and influences junctional organization. These findings suggest a functional pathway through which PD GSC secretomes can modulate BBB permeability, potentially impacting therapeutic efficacy.