Tissue and plasma expression of the angiogenic peptide adrenomedullin in breast cancer

Abstract

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 ¼ 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 ¼ 0.641, P ¼ 0.017). Moreover, ADM levels in breast cancer patients correlated with the presence of lymph node metastasis (P ¼ 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.

Molecular signatures of metaplastic carcinoma of the breast by large-scale transcriptional profiling: identification of genes potentially related to epithelial–mesenchymal transition

“…Several other genes including ADM, ENPP2, PLAGL1 and BMP2 are also related to breast cancer. While ADM and ENPP2, potentially related to angiogenesis, are reportedly overexpressed in breast cancer (Oehler et al, 2003;Jansen et al, 2005), PLAGL1 and BMP2 exhibit tumor suppressor activity in breast cancer based on their growth inhibitory effects and their reduced expression in cancer tissue compared to normal breast tissue (Soda et al, 1998;Bilanges et al, 1999;Reinholz et al, 2002). Despite their potential roles in the conventional type of breast cancer, how these genes participate in the pathophysiology of MCB remains to be clarified.…”

CENP‐F expression is associated with poor prognosis and chromosomal instability in patients with primary breast cancer

“…26 Genes we identified as being highly associated with good prognosis included ER, PR, keratin 18, and serpinA3, a protease inhibitor, 27 as well as lipophilin B and mammaglobin A, which form a heterodimeric complex and are overexpressed in breast cancer, but whose function remains unknown. 28,29 A heatmap was generated that depicts the association of the prognostic genes we identified, with their respective class (Fig.…”

Stat3 upregulates MEK5 expression in human breast cancer cells

“…Another 14 candidate genes that may function in cell growth, cell survival, or tumor angiogenesis are also listed in Table 1. For example, c-fos and 6-phospho-fructo-2-kinase/fructose-2,6-biphosphatatse 3 may participate in promoting cell growth (Atsumi et al, 2002;Kauraniemi et al, 2004); adrenomedullin may be involved in promoting cell survival, angiogenesis, and metastasis (Martinez et al, 2002;Oehler et al, 2002Oehler et al, , 2003; mmp-1, mmp-10, VEGF, and cox-2 play important roles in angiogenesis and metastasis (Ueno et al, 1997;Giambernardi et al, 1998;Niu et al, 2002b;Howe and Dannenberg, 2003;Wei et al, 2003;Tan et al, 2004 We also investigated the other MEK kinase family member, MEK1/2. The result showed that MEK1/2 was not induced by Stat3-C ( Figure 1a).…”