Liquid biopsy targeting monocarboxylate transporter 1 on the surface membrane of tumor-derived extracellular vesicles from synovial sarcoma

The lack of noninvasive biomarkers that can be used for tumor monitoring is a major problem for soft-tissue sarcomas. Here we describe a sensitive analytical technique for tumor monitoring by detecting circulating extracellular vesicles (EVs) of patients with synovial sarcoma (SS). The proteomic analysis of purified EVs from SYO-1, HS-SY-II, and YaFuSS identified 199 common proteins. DAVID GO analysis identified monocarboxylate transporter 1 (MCT1) as a surface marker of SS-derived EVs, which was also highly expressed in SS patient-derived EVs compared with healthy individuals. MCT1⁺CD9⁺ EVs were also detected from SS-bearing mice and their expression levels were significantly correlated with tumor volume (p = 0.003). Furthermore, serum levels of MCT1⁺CD9⁺ EVs reflected tumor burden in SS patients. Immunohistochemistry revealed that MCT1 was positive in 96.7% of SS specimens and its expression on the cytoplasm/plasma membrane was significantly associated with worse overall survival (p = 0.002). Silencing of MCT1 reduced the cellular viability, and migration and invasion capability of SS cells. This work describes a new liquid biopsy technique to sensitively monitor SS using circulating MCT1⁺CD9⁺ EVs and indicates the therapeutic potential of MCT1 in SS.