Cornelison R C, Yuan J X, Tate K M, Petrosky A, Beeghly G F, Bloomfield M, Schwager S C, Berr A L, Stine C A, Cimini D, Bafakih F F, Mandell J W, Purow B W, Horton B J, Munson J M
Department of Biomedical Engineering, University of Massachusetts Amherst, Amherst, MA, 01003, USA.
Department of Biomedical Engineering & Mechanics, Virginia Tech, Blacksburg, VA, 24061, USA.
NPJ Precis Oncol. 2022 Jul 29;6(1):54. doi: 10.1038/s41698-022-00290-8.
Glioblastoma is an aggressive brain cancer characterized by diffuse infiltration. Infiltrated glioma cells persist in the brain post-resection where they interact with glial cells and experience interstitial fluid flow. We use patient-derived glioma stem cells and human glial cells (i.e., astrocytes and microglia) to create a four-component 3D model of this environment informed by resected patient tumors. We examine metrics for invasion, proliferation, and putative stemness in the context of glial cells, fluid forces, and chemotherapies. While the responses are heterogeneous across seven patient-derived lines, interstitial flow significantly increases glioma cell proliferation and stemness while glial cells affect invasion and stemness, potentially related to CCL2 expression and differential activation. In a screen of six drugs, we find in vitro expression of putative stemness marker CD71, but not viability at drug IC, to predict murine xenograft survival. We posit this patient-informed, infiltrative tumor model as a novel advance toward precision medicine in glioblastoma treatment.
胶质母细胞瘤是一种具有弥漫性浸润特征的侵袭性脑癌。浸润的胶质瘤细胞在切除术后仍存在于大脑中，在那里它们与神经胶质细胞相互作用并经历间质液流动。我们使用患者来源的胶质瘤干细胞和人类神经胶质细胞（即星形胶质细胞和小胶质细胞），根据切除的患者肿瘤构建这种环境的四组分三维模型。我们在神经胶质细胞、流体力学和化疗的背景下，研究侵袭、增殖和假定干性的指标。虽然七个患者来源的细胞系的反应具有异质性，但间质流动显著增加了胶质瘤细胞的增殖和干性，而神经胶质细胞影响侵袭和干性，这可能与CCL2表达和差异激活有关。在对六种药物的筛选中，我们发现假定的干性标志物CD71的体外表达，但不是药物半数抑制浓度下的存活率，可预测小鼠异种移植的存活情况。我们认为这种基于患者的浸润性肿瘤模型是胶质母细胞瘤治疗中精准医学的一项新进展。
