FGFR1和FGFR2的空间分布及其与胶质母细胞瘤肿瘤侵袭的功能相关性。
Spatial distribution and functional relevance of FGFR1 and FGFR2 expression for glioblastoma tumor invasion.
发表日期:2023 Aug 12
作者:
Nawal Alshahrany, Ayesha Begum, Dorit Siebzehnrubl, Ana Jimenez-Pascual, Florian A Siebzehnrubl
来源:
CANCER LETTERS
摘要:
胶质母细胞瘤是成年人最致命的脑癌。这些不可治愈的肿瘤具有明显的异质性、抗治疗性和广泛浸润性。这些特点与癌干细胞有关,癌干细胞在胶质母细胞瘤的肿瘤进展和复发中起重要作用。纤维母细胞生长因子受体1(FGFR1)信号通路是胶质母细胞瘤治疗抵抗性和癌干细胞特性的已知调节因子。FGFR1表达存在异肿瘤间异质性,并且高表达与胶质母细胞瘤患者生存期显著较差相关。FGFR1在肿瘤浸润中的作用已在许多癌症中研究过,但FGFR1是否以及如何介导胶质母细胞瘤的浸润还有待确定。在本研究中,我们研究了FGFR1和FGFR2在人胶质母细胞瘤异种移植模型中的分布和功能相关性。我们发现FGFR1在浸润性胶质母细胞瘤细胞中有表达,而FGFR2没有。FGFR1的失去,而非FGFR2,显著减少了体外细胞迁移和人胶质母细胞瘤异种移植瘤的浸润。FGFR1和FGFR2敲除胶质母细胞瘤细胞的RNA测序数据的比较分析揭示了与肿瘤浸润相关的FGFR1特异性基因调节网络。我们的研究揭示了与FGFR1介导的胶质母细胞瘤浸润相关的新基因候选者。版权所有 © 2023,Elsevier B.V.出版。
Glioblastoma is the most lethal brain cancer in adults. These incurable tumors are characterized by profound heterogeneity, therapy resistance, and diffuse infiltration. These traits have been linked to cancer stem cells, which are important for glioblastoma tumor progression and recurrence. The fibroblast growth factor receptor 1 (FGFR1) signaling pathway is a known regulator of therapy resistance and cancer stemness in glioblastoma. FGFR1 expression shows intertumoral heterogeneity and higher FGFR1 expression is associated with a significantly poorer survival in glioblastoma patients. The role of FGFR1 in tumor invasion has been studied in many cancers, but whether and how FGFR1 mediates glioblastoma invasion remains to be determined. Here, we investigated the distribution and functional relevance of FGFR1 and FGFR2 in human glioblastoma xenograft models. We found FGFR1, but not FGFR2, expressed in invasive glioblastoma cells. Loss of FGFR1, but not FGFR2, significantly reduced cell migration in vitro and tumor invasion in human glioblastoma xenografts. Comparative analysis of RNA-sequencing data of FGFR1 and FGFR2 knockdown glioblastoma cells revealed a FGFR1-specific gene regulatory network associated with tumor invasion. Our study reveals new gene candidates linked to FGFR1-mediated glioblastoma invasion.Copyright © 2023. Published by Elsevier B.V.