Elevated expression of adrenomedullin is correlated with prognosis and disease severity in osteosarcoma

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.