Hypoxia-inducible adrenomedullin accelerates hepatocellular carcinoma cell growth.
Adrenomedullin is implicated in tumor progression and induced by hypoxia. We evaluated if adrenomedullin signaling is active in hepatocellular carcinoma (HCC), especially under hypoxic conditions, and to analyze its prognostic implication in HCC patients. HCC cells expressed adrenomedullin and its receptor, and hypoxia induced adrenomedullin expression. Adrenomedullin stimulated HCC cell growth via Akt activation, which was prevented by adrenomedullin peptide inhibitor. Clinico-pathological analysis revealed adrenomedullin extent was related to vascular invasion and N-cadherin intensity, which were reported to indicate a poor prognosis. In conclusion, adrenomedullin signaling is hypoxia-inducible and functionally active in HCCs, and its expression may be a prognostic factor.
Park
Su Cheol
SC
Department of Internal Medicine, Korea Institute of Radiological and Medical Sciences, Korea Cancer Center Hospital, Seoul, Republic of Korea.
Yoon
Jung-Hwan
JH
Lee
Jeong-Hoon
JH
Yu
Su Jong
SJ
Myung
Sun Jung
SJ
Kim
Won
W
Gwak
Geum-Youn
GY
Lee
Sung-Hee
SH
Lee
Soo-Mi
SM
Jang
Ja June
JJ
Suh
Kyung-Suk
KS
Lee
Hyo-Suk
HS
D053607:Adrenomedullin / Q000502:physiology*; D000328:Adult; D001483:Base Sequence; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D017931:DNA Primers; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000473:pathology*; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D017931:DNA Primers; D053607:Adrenomedullin