Correlation of adrenomedullin with the erythropoietin receptor and microvessel density in hepatocellular carcinoma

Introduction Uncontrolled angiogenesis plays an essential role in the occurrence, metastasis and malignant progression of hepatocellular carcinoma (HCC). This study aimed to investigate the expression of adrenomedullin (ADM) in human HCC and its correlation with the expression of erythropoietin receptor (EPOR), microvessel density (MVD) and the tumor pathological characteristics. Material and methods Fresh tumor tissues were obtained from 30 HCC patients after hepatectomy. Ten cirrhotic and 10 normal liver tissues were included as controls. Expression of ADM and EPOR was determined by real-time PCR. The MVD was determined by counting the number of microvessels. Results The MVD and the mRNA levels of ADM and EPOR in cancer tissues were significantly higher than those in the non-cancer tissues (p < 0.05). Expression of ADM was significantly correlated with the MVD and EPOR (r = 0.68 and 0.74, p < 0.01). Adrenomedullin and EPOR mRNA levels in HCC tissues were correlated with capsule invasion, pathological differentiation and tumor metastasis (p < 0.05). Conclusions Our findings suggest that ADM and EPOR may serve as new regulatory factors involved in angiogenesis of HCC and represent novel targets for the treatment of HCC.

[1]  J. Yi,et al.  The histone demethylase JMJD1A regulates adrenomedullin-mediated cell proliferation in hepatocellular carcinoma under hypoxia. , 2013, Biochemical and biophysical research communications.

[2]  A. Januszewicz,et al.  Adrenomedullin concentrations at two time points following myocardial infarction and prediction of mid-term outcomes , 2011, Archives of medical science : AMS.

[3]  G. Gwak,et al.  Hypoxia-inducible adrenomedullin accelerates hepatocellular carcinoma cell growth. , 2008, Cancer letters.

[4]  S. Kawasaki,et al.  Identification of genes associated with multiple nodules in hepatocellular carcinoma using cDNA microarray: multicentric occurrence or intrahepatic metastasis? , 2008, Hepato-gastroenterology.

[5]  H. Friess,et al.  Adrenomedullin is induced by hypoxia and enhances pancreatic cancer cell invasion , 2007, International journal of cancer.

[6]  D. Figarella-Branger,et al.  [Role of adrenomedullin in glioblastomas growth]. , 2005, Bulletin du Cancer.

[7]  Y. Nishimura,et al.  Erythropoietin/Erythropoietin-receptor system as an angiogenic factor in chemically induced murine hepatic tumors , 2004, International Journal of Clinical Oncology.

[8]  N. Weidner,et al.  Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors , 2004, Breast Cancer Research and Treatment.

[9]  M. Arcasoy,et al.  Expression of erythropoietin receptor splice variants in human cancer. , 2003, Biochemical and biophysical research communications.

[10]  E. Crivellato,et al.  Erythropoietin as an angiogenic factor in gastric carcinoma , 2003, Histopathology.

[11]  M. Nakagawa,et al.  Involvement of adrenomedullin induced by hypoxia in angiogenesis in human renal cell carcinoma , 2002, International journal of urology : official journal of the Japanese Urological Association.

[12]  N. Brünner,et al.  Neutralization of adrenomedullin inhibits the growth of human glioblastoma cell lines in vitro and suppresses tumor xenograft growth in vivo. , 2002, The American journal of pathology.

[13]  S. Akiba,et al.  Expression of the adrenomedullin gene in epithelial ovarian cancer. , 2000, Molecular human reproduction.

[14]  T. Mitsui,et al.  Quantitation of sinusoid‐like vessels in hepatocellular carcinoma: Its clinical and prognostic significance , 1997, Hepatology.