Open AccessIntermedin is overexpressed in hepatocellular carcinoma and regulates cell proliferation and survival
Author(s) -
Guo Xiaojia,
Schmitz John C.,
Kenney Barton C.,
Uchio Edward M.,
Kulkarni Sanjay,
Cha Charles H.
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2012.02341.x
Subject(s) - hepatocellular carcinoma , angiogenesis , cancer research , metastasis , cell growth , tumor progression , apoptosis , liver cancer , cancer , biology , medicine , downregulation and upregulation , pathology , biochemistry , genetics , gene
Angiogenesis is one of the hallmarks of tumor growth and metastasis. Identification of tumor angiogenic factors has been a critical component in understanding cancer biology and treatment. Intermedin (IMD) has been reported to promote angiogenesis in a rat ischemic model and human umbilical vascular endothelial cells. Our study sought to determine the role of IMD in human hepatocellular carcinoma tumor progression. High IMD mRNA expression levels were observed in human hepatocellular carcinoma tumors, even in early stage disease, by real‐time RT‐PCR. Immunohistochemical analysis of hepatocellular carcinoma clinical samples demonstrated that the tumor regions were significantly more immunoreactive for IMD than adjacent benign liver. Inhibition of IMD expression using RNA interference reduced cell proliferation in SK‐Hep‐1 and SNU‐398 cells. Blockage of IMD signaling using either an antagonist peptide or a neutralizing antibody inhibited growth in a dose‐dependent manner with concomitant induction of apoptosis, causing cleavage of caspase‐8 and downregulation of Gli1 and Bcl2. Conversely, addition of IMD active peptide increased the phosphorylation level of extracellular signal‐regulated kinase. Thus, IMD might play an important role in cell proliferation and survival of hepatocellular carcinoma. Our data suggests that IMD is a potential biomarker and therapeutic target for hepatocellular carcinoma. ( Cancer Sci , doi: 10.1111/j.1349‐7006.2012.02341.x, 2012)