title: CD47 blockade inhibits tumor progression human osteosarcoma in xenograft models.
abstract: Osteosarcoma is the most common bone tumors in children and adolescents. Despite intensive chemotherapy, patients with advanced disease still have a poor prognosis, illustrating the need for alternative therapies. In this study, we explored the use of antibodies that block CD47 with a tumor growth suppressive effect on osteosarcoma. We first found that up-regulation of CD47 mRNA levels in the tumorous tissues from eight patients with osteosarcoma when compared with that in adjacent non-tumorous tissues. Further western-blot (WB) and immunohistochemistry (IHC) demonstrated that CD47 protein level was highly expressed in osteosarcoma compared to normal osteoblastic cells and adjacent non-tumorous tissues. Osteosarcoma cancer stem cell markers staining shown that the majority of CD44+ cells expressed CD47 albeit with different percentages (ranging from 80% to 99%). Furthermore, high CD47 mRNA expression levels were associated with a decreased probability of progression-free and overall survival. In addition, blockade of CD47 by specific Abs suppresses the invasive ability of osteosarcoma tumor cells and further inhibits spontaneous pulmonary metastasis of KRIB osteosarcoma cells in vivo. Finally, CD47 blockade increases macrophage phagocytosis of osteosarcoma tumor cells.In conclusion, our findings demonstrate that CD47 is a critical regulator in the metastasis of osteosarcoma and suggest that targeted inhibition of this antigen by anti-CD47 may be a novel immunotherapeutic approach in the management of this tumor.
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, PR China.
authors.forename: Ji-Feng
authors.initials: JF
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, PR China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Pan
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, PR China.
authors.forename: Shui-Jun
authors.initials: SJ
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, PR China.
authors.forename: Bin-Song
authors.initials: BS
authors.lastname: Qiu
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, PR China.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Gu
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, PR China.
authors.forename: Jian-Fei
authors.initials: JF
authors.lastname: Hong
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Bi
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, PR China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Wang
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology*; D051928:CD47 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009361:Neoplasm Invasiveness / Q000276:immunology*; D009362:Neoplasm Metastasis / Q000473:pathology*; D012516:Osteosarcoma / Q000401:mortality / Q000473:pathology*; D010587:Phagocytosis / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays
chemical_list: D000906:Antibodies; D051928:CD47 Antigen; D012333:RNA, Messenger
keywords: CD47; antibody; immunotherapy; osteosarcoma