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IMP2/IGF2BP2 expression, but not IMP1 and IMP3, predicts poor outcome in patients and high tumor growth rate in xenograft models of gallbladder cancer

Authors
 Sonja M. Kessler  ;  Eva Lederer  ;  Stephan Laggai  ;  Nicole Golob-Schwarzl  ;  Kevan Hosseini  ;  Johannes Petzold  ;  Caroline Schweiger  ;  Robert Reihs  ;  Marlen Keil  ;  Jens Hoffmann  ;  Christian Mayr  ;  Tobias Kiesslich  ;  Martin Pichler  ;  Kyung Sik Kim  ;  Hyungjin Rhee  ;  Young Nyun Park  ;  Sigurd Lax  ;  Peter Obrist  ;  Alexandra K. Kiemer  ;  Johannes Haybaeck 
Citation
 Oncotarget, Vol.8(52) : 89736-89745, 2017 
Journal Title
 Oncotarget 
Issue Date
2017
Keywords
IGF2BP1/IMP1 ; IGF2BP2/IMP2/p62 ; IGF2BP3/IMP3 ; NADPH oxidase ; gallbladder carcinoma
Abstract
Overexpression of the oncofetal insulin-like growth factor 2 mRNA-binding protein 2 (IMP2/IGF2BP2) has been described in different cancer types. Gallbladder carcinoma (GBC) is a rare but highly aggressive cancer entity with late clinical detection and poor prognosis. The aim of this study was to investigate the role of IMP2 in human GBC. Tissue microarrays (TMAs) of an international multi-center GBC sample collection from n = 483 patients were analyzed by immunohistochemistry. IMP2 immunoreactivity was found in 74.3% of the tumor samples on TMA, of which 14.0% showed strong and 86.0% low staining intensity. 72.4% of the tumor samples were IMP1 positive, but IMP1 showed lower expression in tumor tissue compared to control tissues. IMP3 immunoreactivity was observed in 92.7% of all tumors, of which 53.6% revealed strong IMP3 expression. Kaplan-Meier analysis linked high IMP2 expression to shorter survival time (p = 0.033), whereas neither IMP1 nor IMP3 expression was linked to a decreased survival time. Eight different human biliary tract cancer (BTC) cell lines were evaluated for tumor growth kinetics in mouse xenografts. Cell lines with high IMP2 expression levels showed the fastest increase in tumor volumes in murine xenografts. Furthermore, IMP2 expression in these cells correlated with the generation of reactive oxygen species (ROS) and RAC1 expression in BTC cells, suggesting RAC1-induced ROS generation as a potential mechanism of IMP2-promoted progression of GBC. In conclusion, IMP2 is frequently overexpressed in GBC and significantly associated with poor prognosis and growth rates in vivo. IMP2 might therefore represent a new target for the treatment of advanced GBC.
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DOI
10.18632/oncotarget.21116
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
김경식(Kim, Kyung Sik) ORCID logo https://orcid.org/0000-0001-9498-284X
박영년(Park, Young Nyun) ORCID logo https://orcid.org/0000-0003-0357-7967
이형진(Rhee, Hyungjin) ORCID logo https://orcid.org/0000-0001-7759-4458
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/163847
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