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ADM

adrenomedullin;ADM;adrenomedullin

preproadrenomedullin|proadrenomedullin N-20 terminal peptide

11p15.4

protein-coding

Adrenomedullin (ADM) is an angiogenic factor that has also been shown to be a mitogen and a hypoxia survival factor for tumour cells. These properties point to ADM as a potential promoter of human malignancies, but little data are available concerning the expression of ADM in human breast cancer. In the present work, we have examined ADM peptide expression in a series of malignant breast tumours by immunohistochemistry using a newly developed anti-ADM monoclonal antibody. In addition, ADM plasma concentrations in breast cancer patients and healthy controls were determined by radioimmunoassay. Of the examined breast cancer samples, 27/33 (82%) showed a moderate to strong staining intensity. ADM-peptide expression in breast tumours was significantly correlated with axillary lymph node metastasis (P=0.030). Analysis of ADM plasma concentrations showed no significant difference between the circulating ADM levels of breast cancer patients and healthy controls. However, a significant positive correlation was found between tumour size and plasma ADM levels (r=0.641, P=0.017). Moreover, ADM levels in breast cancer patients correlated with the presence of lymph node metastasis (P=0.002). In conclusion, we have shown for the first time that ADM peptide is widely expressed in breast cancer and that the degree of expression is associated with lymph node metastasis. ADM peptide in plasma of breast cancer patients reflects the size of the primary tumour, but is unlikely to be a useful tumour marker for the detection of breast cancer. Plasma ADM might represent an independent predictor of lymph node metastasis. The clinical implications of these findings remain to be evaluated.

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.