*2.1. Sample Collection and Cell Culture*

Tumor sample and stromal GAMs were collected from our Department of Neurosurgery, Taipei Medical University-Shuang Ho Hospital, under strict adherence to Institutional Review Board (IRB) guidelines (approval numbers: IRB: N201801070 and N201602060). Patients were fully informed and a written consent form was signed prior to the operation. The pathological examination was performed by the Department of Pathology and all verified cases met the criteria of GBM. Samples (tumor samples and stromal cells) were isolated and cultured according to previously established protocols [8,9]. Human GBM cell lines U87MG and LN18 were obtained from the American Type Culture Collection (ATCC) and maintained in DMEM supplemented with 2 mM glutamine, 100 U/mL penicillin, 100 μg/mL streptomycin, and 10% FBS. Neurospheres from both cell lines and clinical samples were generated using tumor-sphere-forming medium containing growth factors supplemented with DMEM-F12 1:1 medium, as previously described [10]. For coculture experiments, a previously established protocol was followed with minor modifications [11]. In brief, U87MG and LN18 (2 <sup>×</sup> <sup>10</sup><sup>5</sup> cells) were seeded in a transwell insert (0.4 <sup>μ</sup>m pore size) with GAMs (2.5 <sup>×</sup> 10<sup>5</sup> cells) seeded in the lower chamber of a six-well system. Cells were cultured in DMEM medium as described above. Cells were maintained for 48 h and harvested for further analyses. In the case of the exosome coculture, GBM cells were cultured in serum-free DMEM in the presence of exosomes for 48 h and harvested.
