肿瘤细胞治疗研究
英文原题：Glioblastoma progression is hindered by melatonin-primed mesenchymal stromal cells through dynamic intracellular and extracellular reorganizations.
Glioblastoma progression is hindered by melatonin-primed mesenchymal stromal cells through dynamic intracellular and extracellular reorganizations.
我们的研究表明，褪黑素增强了MSC的抗癌特性，为它们与GBM细胞和肿瘤环境的相互作用提供了新的见解。
原理：胶质母细胞瘤（GBM）是最致命形式的脑癌，其治疗始终是一项持续挑战。间充质基质细胞（MSC）因其肿瘤归巢能力而被探索作为癌症管理中的治疗工具。然而，由于MSC在癌变中作用存在争议，其临床应用受到限制。本研究探讨MSC如何影响肿瘤行为，并探索与褪黑素（Mel）联合使用的协同抗癌效果。方法：使用原位和皮下GBM异种移植小鼠模型评估Mel预处理的MSC（MSC Mel）的抗肿瘤效果。进行组织学、免疫组织化学和超微结构分析，以识别肿瘤中的表型变化。通过一系列体外试验，包括直接和间接共培养、动态单细胞追踪和肿瘤球试验，我们探索了MSC Mel对原发性和非原发性GBM细胞的影响。转录组分析用于识别该协同疗法调节的基因和通路。结果：MSC Mel延缓了小鼠肿瘤生长并增加了胶原沉积。此外，与未处理的MSC相比，MSC Mel显示出增强的防止GBM细胞迁移的能力。分子分析识别了暴露于MSC Mel的GBM细胞中与细胞迁移、细胞骨架动力学和细胞外基质重塑相关的基因和蛋白质，包括波形蛋白表达降低。最后，识别了与GBM患者临床结局相关的遗传特征。结论：我们的研究表明，褪黑素增强了MSC的抗癌特性，为其与GBM细胞和肿瘤环境的相互作用提供了新见解。这些发现为推进基于MSC的疗法在临床实践中的应用提供了有价值的指导。
Rationale: Glioblastoma (GBM) is the most fatal form of brain cancer and its treatment represents a persistent challenge. Mesenchymal stromal cells (MSCs) have been explored as therapeutic tools in cancer management owing to their tumor-homing abilities. However, their clinical application is limited due to the controversial role of MSCs in carcinogenesis. This study investigates how MSCs influence tumor behavior and explores the synergistic anticancer effects in combination with melatonin (Mel). Methods: Orthotopic and subcutaneous GBM xenograft mouse models were used to assess the antitumor effect of Mel pre-treated MSCs (MSC Mel ). Histological, immunohistochemical, and ultrastructural analyses were conducted to identify phenotypic changes in tumors. Through a set of in vitro assays, including direct and indirect co-cultures, dynamic single-cell tracking and tumorsphere assay, we explored the impact of MSC Mel on primary and non-primary GBM cells. Transcriptomic profiling was used to identify genes and pathways modulated by this synergistic therapy. Results: MSC Mel delayed tumor growth in mice and increased collagen deposition. Additionally, MSC Mel showed enhanced capacity to prevent GBM cell migration compared to untreated MSCs. Molecular analysis identified genes and proteins related to cell migration, cytoskeletal dynamics and extracellular matrix remodeling in GBM cells exposed to MSC Mel , including reduced vimentin expression. Finally, a genetic signature associated with the clinical outcomes of GBM patients was identified. Conclusions: Our study demonstrates that melatonin enhances the anticancer properties of MSCs, providing new insights into their interaction with GBM cells and tumor environment. These findings offer valuable guidance for advancing MSC-based therapies in clinical practice.
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