Bispecific antibody suppresses osteosarcoma aggressiveness through regulation of NF-κB signaling pathway. Issue 6 (June 2017)

• Record Type: Journal Article
• Authors: Yu, Gui-Hua; Li, Ai-Min; Li, Xiang; Yang, Zhong; Peng, Hao
• Is Part Of: Tumor biology. Volume 39:Issue 6(2017)
• Publication Date: 2017-06
• Subjects: Osteosarcoma -- aggressiveness -- BsAbBmi/TRIM -- TRIM-14 -- Bmi-1 -- nuclear factor-κB; Cancer -- Periodicals; Oncology -- Periodicals; Tumors -- Periodicals; 616.994
• DOI: 10.1177/1010428317705572
• Languages: English
• ISSNs: 1010-4283

Abstract

Osteosarcoma is one of the most lethal malignancies, and the prognosis remains dismal due to the paucity of effective therapeutic targets. Bmi-1 and TRIM-14 are associated with the initiation and progression of osteosarcoma, which could promote angiogenesis, invasion, and apoptotic resistance in bone cancer tissue. In this study, we constructed a bispecific antibody of BsAbBmi/TRIM targeting Bmi-1 and TRIM-14 and investigated the therapeutic value in bone carcinoma cells and xenograft mice. Our results showed that Bmi-1 and TRIM-14 expression levels were markedly upregulated correlated with nuclear factor-κB nuclear translocation in bone cancer cells and clinical carcinoma tissues. Results have demonstrated that overexpression of Bmi-1 and TRIM-14 promoted growth, proliferation, aggressiveness, and apoptosis resistance of osteosarcoma cells. BsAbBmi/TRIM administration significantly inhibited nuclear factor-κB expression derived by matrix metalloproteinase–9 promoter. BsAbBmi/TRIM administration inhibited growth of osteosarcoma cells and downregulated Bmi-1 and TRIM-14 expression levels. Data also demonstrated that migration and invasion of osteosarcoma cells were also inhibited by BsAbBmi/TRIM. In addition, results illustrated that BsAbBmi/TRIM inhibited tumor growth and tumorigenicity by blockaded sensor expression in nuclear factor-κB signal pathway. Furthermore, in vivo study showed that BsAbBmi/TRIM treatment markedly inhibited the tumorigenicity and growth of osteosarcoma cells compared to either AbBmi-1 or AbTRIM-14 treatment. Notably, survival of xenograft mice was prolonged by BsAbBmi/TRIM treatment compared to either AbBmi-1 or AbTRIM-14 treatment. In conclusion, these results provided new evidence that BsAbBmi/TRIM inhibited the progression of osteosarcoma, which suggest that BsAbBmi/TRIM may be a novel anti-cancer agent for osteosarcoma therapy.