Park Junseong, Koh Ilkyoo, Cha Junghwa, Oh Yoojung, Shim Jin-Kyoung, Kim Hyejin, Moon Ju Hyung, Kim Eui Hyun, Chang Jong Hee, Kim Pilnam, Kang Seok-Gu
Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Pharmaceuticals (Basel). 2024 Apr 19;17(4):529. doi: 10.3390/ph17040529.
No standardized in vitro cell culture models for glioblastoma (GBM) have yet been established, excluding the traditional two-dimensional culture. GBM tumorspheres (TSs) have been highlighted as a good model platform for testing drug effects and characterizing specific features of GBM, but a detailed evaluation of their suitability and comparative performance is lacking. Here, we isolated GBM TSs and extracellular matrices (ECM) from tissues obtained from newly diagnosed wild-type GBM patients and cultured GBM TSs on five different culture platforms: (1) ordinary TS culture liquid media (LM), (2) collagen-based three-dimensional (3D) matrix, (3) patient typical ECM-based 3D matrix, (4) patient tumor ECM-based 3D matrix, and (5) mouse brain. For evaluation, we obtained transcriptome data from all cultured GBM TSs using microarrays. The LM platform exhibited the most similar transcriptional program to paired tissues based on GBM genes, stemness- and invasiveness-related genes, transcription factor activity, and canonical signaling pathways. GBM TSs can be cultured via an easy-to-handle and cost- and time-efficient LM platform while preserving the transcriptional program of the originating tissues without supplementing the ECM or embedding it into the mouse brain. In addition to applications in basic cancer research, GBM TSs cultured in LM may also serve as patient avatars in drug screening and pre-clinical evaluation of targeted therapy and as standardized and clinically relevant models for precision medicine.
除了传统的二维培养外，目前尚未建立用于胶质母细胞瘤（GBM）的标准化体外细胞培养模型。GBM肿瘤球（TSs）已被视为测试药物效果和表征GBM特定特征的良好模型平台，但缺乏对其适用性和比较性能的详细评估。在这里，我们从新诊断的野生型GBM患者的组织中分离出GBM TSs和细胞外基质（ECM），并在五个不同的培养平台上培养GBM TSs：（1）普通TS培养液培养基（LM），（2）基于胶原蛋白的三维（3D）基质，（3）基于患者典型ECM的3D基质，（4）基于患者肿瘤ECM的3D基质，以及（5）小鼠脑。为了进行评估，我们使用微阵列从所有培养的GBM TSs中获取转录组数据。基于GBM基因、干性和侵袭性相关基因、转录因子活性以及经典信号通路，LM平台表现出与配对组织最相似的转录程序。GBM TSs可以通过易于操作且经济高效的LM平台进行培养，同时保留原始组织的转录程序，而无需补充ECM或将其嵌入小鼠脑中。除了在基础癌症研究中的应用外，在LM中培养的GBM TSs还可作为药物筛选和靶向治疗临床前评估中的患者替身，并作为精准医学的标准化且与临床相关的模型。
