Abstract
Simple SummarySynovial sarcoma (SS) is associated with a high risk of recurrence and poor prognosis, and no biomarker useful in monitoring tumor burden exists. We identified monocarboxylate transporter 1 (MCT1) expressed in extracellular vesicles (EVs) derived from synovial sarcoma as a potential such marker. Circulating levels of MCT1+CD9+ EVs were significantly correlated with tumor volume in a SS mouse model. Serum levels of MCT1+CD9+ EVs reflected tumor burden and treatment response in SS patients. Patients with MCT1 expression on the plasma membrane have significantly worse overall survival than those with nuclear expression. Silencing of MCT1 reduced the malignant phenotype including cellular viability, migration, and invasion of SS cells. MCT1 may thus be a promising novel target for liquid biopsies and a novel therapeutic target.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.
Highlights
Soft-tissue sarcomas (STSs) are a heterogeneous group of malignant tumors of mesenchymal origin with more than 50 histological subtypes [1,2]
In order to confirm the secretion of extracellular vesicles (EVs) from Synovial sarcoma (SS) cell lines, the EVs isolated from AskaSS, HS-SY-II, SYO-1, YaFuSS, and Yamato-SS cell lines by ultracentrifugation were analyzed under transmission electron microscopy (TEM)
TEM revealed that the isolated particles were essentially homogeneous vesicles with sizes ranging from 40–200 nm and with a bilayer goblet structure (Figure 1A)
Summary
Soft-tissue sarcomas (STSs) are a heterogeneous group of malignant tumors of mesenchymal origin with more than 50 histological subtypes [1,2]. STSs constitute a rare group of cancers, comprising less than 1% of all malignancies [3,4,5]. One of the reasons for this is the lack of available biomarkers to monitor the tumor response to multimodal treatment or tumor relapse following definitive treatment. Synovial sarcoma (SS), a high-grade tumor accounting for 6–10% of all STSs, is no exception and represents a high risk of tumor relapse, estimated to be 12% locally and 39% at distant sites [11]. While the presence of chromosomal translocation in tumor specimens has been used for clinical diagnosis, no biomarker that is capable of monitoring tumor burden or treatment response has yet been identified
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