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01.02.2014 | Research Article

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

verfasst von: Yasushi Adachi, 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

Erschienen in: Tumor Biology | Ausgabe 2/2014

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Abstract

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.

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Titel: The effect of IGF-I receptor blockade for human esophageal squamous cell carcinoma and adenocarcinoma
verfasst von: Yasushi Adachi
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
Publikationsdatum: 01.02.2014
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 2/2014
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-013-1131-2

Springer Medizin

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

Abstract

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Springer Medizin

Abstract

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