Elevated expression of adrenomedullin is correlated with prognosis and disease severity in osteosarcoma
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ORIGINAL PAPER
Elevated expression of adrenomedullin is correlated with prognosis and disease severity in osteosarcoma Xing Dai • Wei Ma • Xijing He • Rajiv Kumar Jha
Received: 18 August 2012 / Accepted: 23 August 2012 Ó Springer Science+Business Media New York 2012
Abstract The treatment for osteosarcoma is a formidable challenge. Currently, treatment is not sufficiently effective, and new therapeutic targets are urgently needed. The aim of this study is to determine the expression of adrenomedullin (ADM) in human osteosarcoma tissue and to assess its effect on the proliferation of MG-63 cells and in vivo in an animal model of osteosarcoma. First, we collected clinical specimens from osteosarcoma patients and healthy controls and measured ADM expression by immunohistochemistry, RT-PCR, and radioimmunoassay. We also analyzed clinical data to investigate the relationship between ADM expression, malignancy, and tumor prognosis. Based on these data, we used RNA interference (RNAi) against ADM delivered by lentivirus vector transfected into the osteosarcoma cell line MG-63 to downregulate the expression of ADM. Finally, we observed the effect of ADM on the proliferation of MG-63 cells in vitro, and in vivo, in an animal model of osteosarcoma. We found that ADM was overexpressed in human osteosarcoma tissue, whereas expression was low in the adjacent tissue and little expression was observed in normal tissue. ADM RNAi significantly inhibited the proliferation of MG-63 cells. Therefore, the growth of osteosarcoma could be inhibited by decreasing the expression of ADM. Thus, we conclude that ADM expression is highly correlated with the degree of malignancy and metastasis of osteosarcoma.
X. Dai X. J. He (&) Second Department of Orthopedic Surgery, Second Affiliated Hospital of Medical College, Xi’an Jiaotong University, 157 West Five Road, Xi’an 710004, Shaanxi, China e-mail: [email protected] W. Ma R. K. Jha Department of Orthopedic Surgery, First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710004, Shaanxi, China
Keywords MG-63
Osteosarcoma Adrenomedullin RNAi
Introduction Osteosarcoma is one of the most common primary malignant bone tumors with highly malignant and invasive growth characteristics. With traditional treatment methods, such as chemotherapy, wide tumor resection, and amputation, patients have a poor prognosis, with 5-year survival rates less than 20 % [1]. In recent years, extensive applications of neoadjuvant chemotherapy and limb salvage surgery have yielded great improvements in the 5-year survival rates and quality of life of osteosarcoma patients [2]. However, the overall prognosis of osteosarcoma has not significantly improved as a result [3]. Recently, it has seemed impossible to improve the poor prognosis associated with osteosarcoma, and the fact that 75 % of osteosarcoma cases occur in 10- to 20-year-old patients makes this disease a great burden to families and society. Therefore, it is extremely important to find key proteins or genes that predict the
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