SYT-SSX1 enhances the invasiveness and maintains stem-like cell properties in synovial sarcoma via induction of TGF-\u03b21/Smad signaling

Yan Qi,Zhong Li,Jian-Ming Hu,Xiao Feng,Hong Zou,Ya-Lan Huang,Li-Juan Pang,Mei Er Tu He Ta Mi Shi Shi,Shuang-Shuang Dong,Yong-Lai He,Zi-Han Liu,Qing Yao,Zhen Zhang,Feng Li,Ning Wang

doi:10.1186/s12885-022-09229-5

Abstract

BackgroundSynovial sarcoma (SS) is a type of soft tissue sarcoma (STS) of undetermined tissue origin, which is characterized by the recurrent pathognomonic chromosomal translocation t (X;18)(p11.2; q11.2). Studies have shown that SS is a malignant tumor originating from cancer stem cells or pluripotent mesenchymal stem cells and may be related to fusion genes. In addition, some studies have indicated that the induction of epithelial–mesenchymal transition (EMT) via the TGF-β1/Smad signaling pathway leads to SS metastasis.MethodsWe analyzed the effects of SYT-SSX1 on the stemness of SS cells via TGF-β1/Smad signaling in vitro. The SYT-SSX1 fusion gene high expression cell was constructed by lentiviral stable transfer technology. SYT-SSX1 and SW982 cells were cultured and tested for sphere-forming ability. The transwell migration assay and flow cytometry were used to assess the migration ability of the sphere cells as well as the expression of CSC-related markers. We treated SYT-SSX1 cells with rhTGF-β1 (a recombinant agent of the TGF-β1 signaling pathway) and SB431542 and observed morphological changes. A CCK-8 experiment and a western blot (WB) experiment were conducted to detect the expression of TGF-β1 signaling pathway- and EMT-related proteins after treatment. The SYT-SSX1 cells were then cultured and their ability to form spheres was tested. Flow cytometry, WB, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of CSC surface markers on SYT-SSX1 sphere cells.ResultsIt was found that SYT-SSX1 has stronger sphere-forming ability, migration ability, and higher expression of CSC-related molecules than SW982 cells. Through treating SYT-SSX1 and SW982 cells with rhTGF-β1 and SB431542, we found that TGF-β1 enhanced the proliferation of cells, induced EMT, and that TGF-β1 enhanced the characteristics of tumor stem cells.ConclusionsOur results suggest that SYT-SSX1 enhances invasiveness and maintains stemness in SS cells via TGF-β1/Smad signaling. These findings reveal an effective way to potentially improve the prognosis of patients with SS by eliminating the characteristics of cancer stem cells (CSCs) during treatment.

Highlights

Synovial sarcoma (SS) is a type of soft tissue sarcoma (STS) of undetermined tissue origin, which is char‐ acterized by the recurrent pathognomonic chromosomal translocation t (X;18)(p11.2; q11.2)
Qi et al BMC Cancer (2022) 22:166 we found that TGF-β1 enhanced the proliferation of cells, induced epithelial–mesenchymal transition (EMT), and that TGF-β1 enhanced the characteristics of tumor stem cells
Our results suggest that SYT-SSX1 enhances invasiveness and maintains stemness in SS cells via TGFβ1/Smad signaling

Summary

Introduction

Synovial sarcoma (SS) is a type of soft tissue sarcoma (STS) of undetermined tissue origin, which is char‐ acterized by the recurrent pathognomonic chromosomal translocation t (X;18)(p11.2; q11.2). Studies have shown that SS is a malignant tumor originating from cancer stem cells or pluripotent mesenchymal stem cells and may be related to fusion genes. Synovial sarcoma (SS) is a highly aggressive malignant tumor of mesenchymal origin and is the fourth most common type of soft tissue sarcoma (STS), accounting for approximately 5–10% of all STSs [1]. Recent studies have shown that SS may originate from cancer stem cells (CSCs) or pluripotent mesenchymal stem cells [2, 3]. Surgical resection is the first choice for treatment followed by postoperative adjuvant radiotherapy and chemotherapy [5, 6]

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Conclusion