American Association for Cancer Research
15357163mct150669-sup-154009_2_supp_3320073_c1c1cc.ppt (609 kB)

Supplemental Table 1 from Bortezomib Inhibits Giant Cell Tumor of Bone through Induction of Cell Apoptosis and Inhibition of Osteoclast Recruitment, Giant Cell Formation, and Bone Resorption

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posted on 2023-04-03, 15:52 authored by Leqin Xu, Jian Luo, Rongrong Jin, Zhiying Yue, Peng Sun, Zhengfeng Yang, Xinghai Yang, Wei Wan, Jishen Zhang, Shichang Li, Mingyao Liu, Jianru Xiao

Epidemiological, clinical, and pathological characteristics of 52 GCTB patients


National Basic Research Program of China

National Natural Science Foundation of China

Innovation Program of Shanghai Municipal Education Commission

Science and Technology Commission of Shanghai Municipality



Giant cell tumor of bone (GCTB) is a rare and highly osteolytic bone tumor that usually leads to an extensive bone lesion. The purpose of this study was to discover novel therapeutic targets and identify potential agents for treating GCTB. After screening the serum cytokine profiles in 52 GCTB patients and 10 normal individuals using the ELISA assay, we found that NF-κB signaling–related cytokines, including TNFα, MCP-1, IL1α, and IL17A, were significantly increased in GCTB patients. The results were confirmed by IHC that the expression and activity of p65 were significantly increased in GCTB patients. Moreover, all of the NF-κB inhibitors tested suppressed GCTB cell growth, and bortezomib (Velcade), a well-known proteasome inhibitor, was the most potent inhibitor in blocking GCTB cells growth. Our results showed that bortezomib not only induced GCTB neoplastic stromal cell (NSC) apoptosis, but also suppressed GCTB NSC–induced giant cell differentiation, formation, and resorption. Moreover, bortezomib specifically suppressed GCTB NSC–induced preosteoclast recruitment. Furthermore, bortezomib ameliorated GCTB cell–induced bone destruction in vivo. As a result, bortezomib suppressed NF-κB–regulated gene expression in GCTB NSC apoptosis, monocyte migration, angiogenesis, and osteoclastogenesis. Particularly, the inhibitory effects of bortezomib were much better than zoledronic acid, a drug currently used in treating GCTB, in our in vitro experimental paradigms. Together, our results demonstrated that NF-κB signaling pathway is highly activated in GCTB, and bortezomib could suppress GCTB and osteolysis in vivo and in vitro, indicating that bortezomib is a potential agent in the treatment of GCTB. Mol Cancer Ther; 15(5); 854–65. ©2016 AACR.

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