Förster Nanna, Isosaari Lotta, Kulta Oskari, Junnila Oona, Vuolanto Valtteri, Pollari Marjukka, Rautajoki Kirsi J, Narkilahti Susanna
NeuroGroup, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Department of Oncology, Tays Cancer Center, Tampere University Hospital, Tampere, Finland.
FASEB J. 2025 Apr 30;39(8):e70567. doi: 10.1096/fj.202500291RR.
Glioblastoma (GB) cells actively interact with the central nervous system (CNS) tumor microenvironment (TME). These interactions, particularly with neurons, require a better understanding. 3D tumor models replicating the human TME are needed to unravel pathological processes and to test novel treatments for efficacy and safety. We developed a novel 3D human coculture model for studying neuron-GB interactions. The model revealed both structural and functional interactions between cell types. Paracrine communication in the coculture model favored a tumor-supportive environment. Notably, cell-specific calcium signaling characteristics differed in cocultures compared to monocultures, highlighting the impact of interactions on cellular functionality in TME. The safety of a clinically used treatment, temozolomide, was tested in the 3D coculture model, and it selectively inhibited GB invasion while preserving neurons' morphology and functionality. The established model provides a tool for dissecting the interactions within the TME and testing the efficacy and safety of novel treatments.
胶质母细胞瘤（GB）细胞与中枢神经系统（CNS）肿瘤微环境（TME）积极相互作用。这些相互作用，尤其是与神经元的相互作用，需要更好地理解。需要复制人类TME的三维肿瘤模型来阐明病理过程，并测试新疗法的疗效和安全性。我们开发了一种用于研究神经元与GB相互作用的新型三维人类共培养模型。该模型揭示了细胞类型之间的结构和功能相互作用。共培养模型中的旁分泌通讯有利于肿瘤支持环境。值得注意的是，与单培养相比，共培养中细胞特异性钙信号特征有所不同，突出了相互作用对TME中细胞功能的影响。在三维共培养模型中测试了临床使用的治疗药物替莫唑胺的安全性，它选择性地抑制GB侵袭，同时保留神经元的形态和功能。所建立的模型为剖析TME内的相互作用以及测试新疗法的疗效和安全性提供了一种工具。
