Label-free sensing of exosomal MCT1 and CD147 for tracking metabolic reprogramming and malignant progression in glioma

Abstract

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.

Circular RNA ZNF609 promotes the malignant progression of glioma by regulating miR-1224-3p/PLK1 signaling

“…Glioma is a prevalent intracranial malignancy contributes to considerable cancer-related mortality 6 , 27 . Meanwhile, it is characterized by insensitive to conventional chemo-radiotherapy 28 , 29 .…”

“…Incidence and mortality of glioma appear to be increasing rapidly in the past few decades as a result of this highly metastatic disease [4,5]. Although the recent treatments like targeted biologic therapy and adjuvant radiotherapy have been markedly improved, overall patient survival is not satisfactory as a result of local recurrence and distant metastasis [6,7]. Thus, identification of potential pathogenic mechanisms of glioma and therapeutic approaches against glioma are significantly indispensable.…”

Liquid Biopsy Targeting Monocarboxylate Transporter 1 on the Surface Membrane of Tumor-Derived Extracellular Vesicles from Synovial Sarcoma

“…In spite of the small sample size, we found that the circulating MCT1 + CD9 + EVs in the serum reflected the tumor burden or treatment response in vivo, indicating the potential for the translation of this liquid biopsy into clinics for the management of SS. MCT1 was recently identified in exosomes derived from malignant glioma cells [ 47 ]. Thakur et al identified MCT1 mainly in the membrane of exosomes, and observed higher MCT1 expression in serum-derived exosomes from a mouse model of glioma compared to those of wild-type mice [ 47 ].…”

“…MCT1 was recently identified in exosomes derived from malignant glioma cells [ 47 ]. Thakur et al identified MCT1 mainly in the membrane of exosomes, and observed higher MCT1 expression in serum-derived exosomes from a mouse model of glioma compared to those of wild-type mice [ 47 ]. These findings are consistent with our data, strongly suggesting that the detection of MCT1 on circulating serum could improve diagnosis and tumor monitoring of SS.…”

Factors Affecting Extracellular Vesicles Based Drug Delivery Systems

“…Extracellular vesicles (EVs) are natural nanovesicles released from most cells and biofluids; they carry various cargo including nucleic acids, proteins, and lipids [ 17 ]. EVs have attracted tremendous attention in the context of NDDS due to their ability to facilitate intracellular communication and the transportation of cargo to the target recipient cells [ 18 , 19 ]. Based on their size range and biogenesis, EVs are categorized into three major types, namely exosomes, microvesicles (MVs), and apoptotic bodies (ABs) [ 20 ].…”