中国重庆大学和重庆总医院的研究团队发现，胶质母细胞瘤肿瘤周围的高粘度液体环境会使脑癌细胞变小、更灵活，更容易入侵周围健康脑组织1。研究人员开发了创新型开放式微流控芯片，揭示了这一物理环境驱动的细胞行为改变机制，相关成果已发表在《Microsystems & Nanoengineering》杂志上1。
研究表明，胶质母细胞瘤肿瘤边缘的液体粘度约为中心坏死组织液体粘度的8倍（7.1 cP）1。两种人类胶质母细胞瘤细胞系（U-251和LN-229）在高粘度环境中适应一个月后，运动速度更快、覆盖距离更远，同时变得更小更易变形，能够通过微流控芯片中的狭窄间隙1。其中U-251细胞激活了CD44、FN1和MMP9等入侵相关基因，表现为间充质样重编程；而LN-229细胞主要表现为物理形态改变，基因表达变化不显著1。
更值得注意的是，这些适应性改变即使在细胞转移回正常粘度液体后仍可检测到，表明改变具有持久性1。研究中观察到YAP蛋白在细胞核内积累，表明细胞已激活了对物理应力的响应通路1。这一发现为理解脑癌扩散提供了新的视角，提示液体粘度作为物理微环境因素在肿瘤侵袭中的关键作用1。该研究获得了国家自然科学基金等多项资助1。
Researchers from Chongqing University and Chongqing General Hospital have identified a critical mechanism by which glioblastoma cells adapt to their environment and become more invasive. The team discovered that the high-viscosity fluid surrounding glioblastoma tumors causes brain cancer cells to become smaller and more flexible, enabling them to infiltrate surrounding healthy brain tissue more effectively.1 Using an innovative open microfluidic chip platform, the scientists demonstrated that these adaptive changes persist even after cells return to normal viscosity environments, suggesting a previously unknown pathway for brain cancer spread.1
The study found that the fluid viscosity at the tumor's edge is approximately eight times higher than that in the necrotic center, measuring 7.1 centipoise.1 After one month of exposure to high-viscosity conditions, two human glioblastoma cell lines—U-251 and LN-229—exhibited increased motility and traveled greater distances.1 The adapted cells became smaller and more deformable, allowing them to pass through narrow gaps in the microfluidic device.1 Analysis revealed that YAP protein accumulated in cell nuclei, indicating activation of physical stress response pathways.1 The U-251 cell line underwent mesenchymal-like reprogramming with activation of invasion-related genes including CD44, FN1, and MMP9, while LN-229 cells primarily displayed physical morphological changes without significant gene expression alterations.1 Notably, protein changes remained detectable after cells were returned to normal viscosity conditions, demonstrating the durability of these adaptive modifications.1 The findings were published in Microsystems & Nanoengineering and supported by grants from the National Natural Science Foundation of China and other funding sources.1
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