Tumor Biology

, Volume 35, Issue 2, pp 973–985 | Cite as

The effect of IGF-I receptor blockade for human esophageal squamous cell carcinoma and adenocarcinoma

  • Yasushi AdachiEmail author
  • Hirokazu Ohashi
  • Arisa Imsumran
  • Hiroyuki Yamamoto
  • Yasutaka Matsunaga
  • Hiroaki Taniguchi
  • Katsuhiko Nosho
  • Hiromu Suzuki
  • Yasushi Sasaki
  • Yoshiaki Arimura
  • David P Carbone
  • Kohzoh Imai
  • Yasuhisa Shinomura
Research Article


Insulin-like growth factor-I receptor (IGF-IR) signaling is required for carcinogenicity and tumor development, and this pathway has not been well studied in human esophageal carcinomas. Esophageal cancer is one of the human cancers with the worst prognosis and has two main histologies: squamous cell carcinomas (ESCC) and adenocarcinoma (EAC). Previously, we have reported that detection of the IGF axis may be useful for the prediction of recurrence and poor prognosis of ESCC. We have also shown the successful therapy for several gastrointestinal cancers using recombinant adenoviruses expressing dominant negative IGF-IR (ad-IGF-IR/dn). The aim of this study is to develop potential targeted therapeutics to IGF-IR and to assess the effect of IGF-IR blockade in both of these types of esophageal cancer. We determined immunohistochemical expression of IGF-IR in a tissue microarray. We then assessed the effect of IGF-IR blockade on signal transduction, proliferation, apoptosis, and motility. Ad-IGF-IR/dn, a tyrosine kinase inhibitor, BMS-536924, and adenovirus expressing shRNA for IGF-IR were used. IGF-IR expression was common in both tumor types but not in normal tissues. IGF-IR was detected in metastatic sites at similar levels compared to the primary site. IGF-IR inhibition suppressed proliferation and colony formation in both cancers. IGF-IR blockades up-regulated both stress- and chemotherapy-induced apoptosis and reduced migration. Although IGF-IR/dn blocked ligand-induced activation of Akt-1 mainly, BMS-536924 effectively blocked both activation of Akt and MAPK. The IGF axis might play a key role in tumor progression of esophageal carcinomas. The IGF-IR targeting strategies might thus be useful anticancer therapeutics for human esophageal malignancies.


Dominant negative EAC ESCC IGF-IR TKI 



Adenovirus expressing IGF-IR /482st


Adenovirus expressing IGF-IR/950st

ad-shIG F-IR

Adenovirus expressing short-hairpin IGF-IR


NH2 terminally truncated IGF-I


Dominant negative


Esophageal adenocarcinoma


Esophageal squamous cell carcinoma


Extracellular signal-regulated kinase


Insulin-like growth factor


IGF binding protein


IGF-I receptor


Truncated IGF-IR of 482 amino acid long


Truncated IGF-IR of 950 amino acid long


Dominant negative form of IGF-IR


Insulin receptor


Monoclonal antibody


Phosphatidylinositide 3-kinase


Tyrosine kinase inhibitor



This work was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology and from the Ministry of Health, Labor and Welfare, Japan. This work was also supported by a grant from the Japanese Society of Strategies for Cancer Research and Therapy.

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Yasushi Adachi
    • 1
    Email author
  • Hirokazu Ohashi
    • 1
  • Arisa Imsumran
    • 1
  • Hiroyuki Yamamoto
    • 1
  • Yasutaka Matsunaga
    • 1
  • Hiroaki Taniguchi
    • 2
  • Katsuhiko Nosho
    • 1
  • Hiromu Suzuki
    • 1
  • Yasushi Sasaki
    • 1
  • Yoshiaki Arimura
    • 1
  • David P Carbone
    • 3
  • Kohzoh Imai
    • 1
    • 2
  • Yasuhisa Shinomura
    • 1
  1. 1.First Department of Internal MedicineSapporo Medical UniversitySapporoJapan
  2. 2.The Institute of Medical ScienceThe University of TokyoTokyoJapan
  3. 3.James Thoracic CenterThe Ohio State UniversityColumbusUSA

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