Malignant glioma is a fatal brain tumor whose pathological progression is closely associated with glycolytic reprogramming, leading to the high expression of monocarboxylate transporter 1 (MCT1) and its ancillary protein, cluster of differentiation 147 (CD147) for enhancing lactate efflux. In particular, malignant glioma cells (GMs) release tremendous number of exosomes, nanovesicles of 30 to 200 nm in size, promoting tumor progression by the transport of pro-oncogenic molecules to neighboring cells. In the present study, we found that hypoxia-induced malignant GMs strongly enhanced MCT1 and CD147 expression, playing a crucial role in promoting calcium-dependent exosome release. Furthermore, it was first identified that hypoxic GMs-derived exosomes contained significantly high levels of MCT1 and CD147, which could be quantitatively detected by noninvasive localized surface plasmon resonance and atomic force microscopy biosensors, demonstrating that they could be precise surrogate biomarkers for tracking parent GMs’ metabolic reprogramming and malignant progression as liquid biopsies.

恶性胶质瘤是一种致命性脑肿瘤，其病理进展与糖酵解重编程密切相关，导致单羧酸转运蛋白 1 (MCT1) 及其辅助蛋白分化簇 147 (CD147) 高表达，从而增强乳酸流出。特别是，恶性神经胶质瘤细胞（GM）释放大量的外泌体，即大小为 30 至 200 nm 的纳米囊泡，通过将促癌分子运输到邻近细胞来促进肿瘤进展。在本研究中，我们发现缺氧诱导的恶性GM强烈增强MCT1和CD147的表达，在促进钙依赖性外泌体释放中发挥关键作用。此外，首次发现低氧GMs衍生的外泌体含有显着高水平的MCT1和CD147，可以通过非侵入性局部表面等离振子共振和原子力显微镜生物传感器定量检测，证明它们可以作为追踪亲本GMs的精确替代生物标志物液体活检中的代谢重编程和恶性进展。