TRAIL-R1 as a novel surface marker for circulating giant cell tumor of bone.

Bai-Chuan Wang,Xian-Lin Zeng,Xiao-Dong Guo,Tong-Chuan He,Yu-Kun Zhang,Zhi-Cai Zhang,Fei-Fei Pu,Jian-Xiang Liu,Shu-Hua Yang,Zeng-Wu Shao

doi:10.18632/oncotarget.17042

TRAIL-R1 as a novel surface marker for circulating giant cell tumor of bone.

Bai-Chuan Wang, Xian-Lin Zeng + Show 8 more

Open Access

https://doi.org/10.18632/oncotarget.17042

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Abstract

Giant cell tumor of bone (GCT), which frequently occurs in the patients’ spine, is relatively prevalent in Chinese population. A group of GCT invades into vessels and appears to be circulating tumor cells (CTCs) responsible for the distal metastasis of the primary tumor. So far the cell surface markers of GCT have not been determined. In the current study, we aimed to identify a novel CTC marker with higher specificity in GCT. TRAIL-R1+ cells were purified from GCT cell lines. The TRAIL-R1+ cells were compared with total GCT cells for tumor sphere formation, chemo-resistance, tumor formation in nude mice, and frequency of developing distal metastases. We found that TRAIL-R1+ GCT cells appeared to be highly enriched for CTCs in GCT. Compared to total GCT cells, TRAIL-R1+ GCT cells generated significantly more tumor spheres in culture, were higher chemo-resistant, and had a higher frequency of being detected in the circulation after subcutaneous transplantation as well as development of distal metastases. Thus, we conclude that TRAIL-R1+ may be a novel CTC marker in GCT. Selective elimination of TRAIL-R1+ GCT cells may improve the current GCT therapy.

Highlights

Giant cell tumors of bone (GCT) are rare bone tumors worldwide, but relatively prevalent in Chinese population [1]
We found that TNF-related apoptosis-inducing ligand (TRAIL)-R1+ Giant cell tumor of bone (GCT) cells appeared to be highly enriched for circulating tumor cells (CTCs) in GCT
We found that compared to TRAIL-R1- cells, TRAIL-R1+ cells appeared to be more resistant to denosumab, since higher cell viability was detected in TRAIL-R1+ cells in either line in an CCK-8 assay (Figure 3C)

Summary

Introduction

Giant cell tumors of bone (GCT) are rare bone tumors worldwide, but relatively prevalent in Chinese population [1]. Most GCT appear to be benign connective tissue neoplasms, which consist of osteoclast-like giant cells, stromal cells, and tumor associated monocytes/macrophages [2]. The stromal cells represent the neoplastic component of the tumor, due to their capacity of propagation, proliferation and invasion to peripheral tissue [3]. Chemotherapy is an important method to assist radiotherapy for treating GCT [4]. Denosumab is a novel and effective treatment for aggressive and recurrent GCT [5, 6]. Since not all GCT cells are sensitive to denosumab, it is important to figure out the mechanisms underlying the chemo-resistance of these GCT cells [7]

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