CD151-mediated adhesion is crucial to osteosarcoma pulmonary metastasis
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Zhuoying Wang1,*, Chongren Wang1,*, Zifei Zhou1,*, Mengxiong Sun1, Chenghao Zhou2, Jian Chen2, Fei Yin2, Hongsheng Wang2, Binhui Lin1, Dongqing Zuo2, Suoyuan Li2, Lijin Feng3, Zhenfeng Duan4, Zhengdong Cai1,2, Yingqi Hua1,2
1Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China
2Shanghai Bone Tumor Institution, Shanghai, 201620, China
3Department of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, China
4Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA
*These authors have contributed equally to this work
Zhengdong Cai, email: firstname.lastname@example.org
Yingqi Hua, email: email@example.com
Keywords: osteosarcoma, tetraspanin, CD151, metastasis, adhesion
Received: December 25, 2015 Accepted: July 26, 2016 Published: August 19, 2016
CD151, a tetraspanin family protein involved in cell-cell and cell-extracellular matrix interaction, is differentially expressed in osteosarcoma cell membranes. Thus, this study aimed to investigate the role of CD151 in osteosarcoma metastasis. We analyzed CD151 expression in patient tissue samples using immunohistochemistry. CD151 expression was also silenced with shRNA in osteosarcoma cells of high metastatic potential, and cell adhesion, migration and invasion were evaluated in vitro and pulmonary metastasis was investigated in vivo. Mediators of cell signaling pathways were also examined following suppression of CD151 expression. Overall survival for patients with low versus high CD151 expression level was 94 vs. 41 months (p=0.0451). CD151 expression in osteosarcoma cells with high metastatic potential was significantly higher than in those with low metastatic potential (p<0.001). shRNA-mediated silencing of CD151 did not influence cell viability or proliferation; however, cell adhesion, migration and invasion were all inhibited (all p<0.001). In mice inoculated with shRNA-transduced osteosarcoma cells, the number and size of lung metastatic lesions were reduced compared to the mice inoculated with control-shRNA transduced cells (p<0.001). In addition, CD151 knockdown significantly reduced Akt, p38, and p65 phosphorylation as well as focal adhesion kinase, integrin β1, p70s6, and p-mTOR levels. Taken together, CD151 induced osteosarcoma metastasis likely by regulating cell function through adhesion signaling. Further studies are necessary to fully explore the diagnostic and prognostic value of determining CD151 expression in osteosarcoma patients.
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