KR158 spheres harboring slow-cycling cells recapitulate GBM features in an immunocompetent system.
KR158 spheres harboring slow-cycling cells recapitulate GBM features in an immunocompetent system.
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含有慢循环细胞的 KR158 球体再现了免疫活性系统中的 GBM 特征。
DOI：
10.1101/2024.01.26.577279
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Deleyr
中科院分区：
文献类型：
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作者：
Chakraborty,Avirup;Yang,Changlin;Kresak,JesseL;Silver,Aryeh;Feier,Diana;Tian,Guimei;Andrews,Michael;Sobanjo,OlusegunO;Hodge,EthanD;Engelbart,MiaK;Huang,Jianping;Harrison,JeffreyK;Sarkisian,MatthewR;Mitchell,DuaneA;Deleyr
胶质母细胞瘤（GBM）由于其侵袭性、异质性和对治疗的耐药性，在临床肿瘤学中提出了重大挑战。肿瘤干细胞（Cancer stem cells, CSCs）在GBM中起着至关重要的作用，特别是在治疗抵抗和肿瘤复发中，强调了了解这些细胞的调节机制的必要性。此外，它们对肿瘤微环境（TME）的多方面贡献强调了它们的重要性，这是由它们独特的性质驱动的。本研究旨在在免疫活性小鼠GBM模型中表征胶质母细胞瘤干细胞（GSCs），特别是慢循环细胞（SCCs），以探索其与人类同类细胞的相似性。使用KR158小鼠模型，我们证实从该模型中分离的SCCs具有类似于人类SCCs的关键特征和功能特性。KR158小鼠SCCs在胶质球实验中扩增，表现出球状形成能力、自我更新能力、阳性致瘤性、增强的干性和对化疗的耐药性。总之，我们的研究结果验证了KR158小鼠模型作为研究gbm病理中GSCs和SCCs的框架，并专门探索scc -免疫系统通信，了解它们在疾病进展中的作用，并评估针对这些特定连接的治疗策略的效果。
Glioblastoma (GBM) poses a significant challenge in clinical oncology due to its aggressive nature, heterogeneity, and resistance to therapies. Cancer stem cells (CSCs) play a critical role in GBM, particularly in treatment-resistance and tumor relapse, emphasizing the need to comprehend the mechanisms regulating these cells. Also, their multifaceted contributions to the tumor-microenvironment (TME) underline their significance, driven by their unique properties. This study aimed to characterize glioblastoma stem cells (GSCs), specifically slow-cycling cells (SCCs), in an immunocompetent murine GBM model to explore their similarities with their human counterparts. Using the KR158 mouse model, we confirmed that SCCs isolated from this model exhibited key traits and functional properties akin to human SCCs. KR158 murine SCCs, expanded in the gliomasphere assay, demonstrated sphere forming ability, self-renewing capacity, positive tumorigenicity, enhanced stemness and resistance to chemotherapy. Together, our findings validate the KR158 murine model as a framework to investigate GSCs and SCCs in GBM-pathology, and explore specifically the SCC-immune system communications, understand their role in disease progression, and evaluate the effect of therapeutic strategies targeting these specific connections.