| RRC ID |
44637
|
| 著者 |
Adachi Y, Ohashi H, Imsumran A, Yamamoto H, Matsunaga Y, Taniguchi H, Nosho K, Suzuki H, Sasaki Y, Arimura Y, Carbone DP, Imai K, Shinomura Y.
|
| タイトル |
The effect of IGF-I receptor blockade for human esophageal squamous cell carcinoma and adenocarcinoma.
|
| ジャーナル |
Tumour Biol
|
| 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.
|
| 巻・号 |
35(2)
|
| ページ |
973-85
|
| 公開日 |
2014-2-1
|
| DOI |
10.1007/s13277-013-1131-2
|
| PMID |
24026884
|
| MeSH |
Adenocarcinoma / genetics*
Adenocarcinoma / pathology
Adenocarcinoma / therapy
Adenoviridae
Carcinogenesis
Carcinoma, Squamous Cell / genetics*
Carcinoma, Squamous Cell / pathology
Carcinoma, Squamous Cell / therapy
Cell Line, Tumor
Esophageal Neoplasms / genetics*
Esophageal Neoplasms / pathology
Esophageal Neoplasms / therapy
Esophageal Squamous Cell Carcinoma
Gene Expression Regulation, Neoplastic
Humans
Insulin-Like Growth Factor I / antagonists & inhibitors
Insulin-Like Growth Factor I / biosynthesis
Insulin-Like Growth Factor I / genetics*
Molecular Targeted Therapy*
Prognosis
Receptor, IGF Type 1 / biosynthesis
Receptor, IGF Type 1 / genetics*
Signal Transduction / genetics
|
| IF |
3.65
|
| 引用数 |
13
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
TE-1(RCB1894)
TE-8(RCB2098) |
