Insulin-like growth factor-I receptor as a marker for prognosis and a therapeutic target in human esophageal squamous cell carcinoma

Arisa Imsumran, Yasushi Adachi, Hiroyuki Yamamoto, Rong Li, Yu Wang, Yongfen Min, Wenhua Piao, Katsuhiko Nosho, Yoshiaki Arimura, Yasuhisa Shinomura, Masao Hosokawa, Choon Taek Lee, David P. Carbone, Kohzoh Imai

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Abstract

Insulin-like growth factor (IGF)-I receptor (IGF-Ir) signaling is required for tumorigenicity and progression of many tumors but this pathway has not been well studied as a prognostic factor or potential therapeutic target in esophageal squamous cell carcinoma (ESCC). In this paper, the association between the expression of IGF-Ir and IGF-II ligand and prognosis was investigated immunohistochemically in 100 surgically resected ESCC.We then assessed the therapeutic effect of blocking IGF receptor signaling using dominant negative IGF-Ir (IGF-Ir/ dn) in ESCC in vitro. Expression of IGF-Ir and IGF-II were detected in 60 and 50% of tumors, respectively, and were associated with invasion depth, metastasis, advanced tumor stage and recurrence. Patients with tumors expressing both IGF-Ir and IGF-II had a significantly shorter survival than those expressing either alone or neither in both single and multivariate analysis. IGF-Ir/dn suppressed proliferation and motility as well as upregulating chemotherapyinduced apoptosis through blocking ligand-induced Akt activation. We propose that detection of IGF-Ir/IGF-II in ESCC may be useful for the prediction of recurrence and poor prognosis and for selecting patients for IGF-Ir-targeted therapy. Therapeutic blockade of IGF-Ir may be a useful anticancer therapeutic for ESCC.

Original languageEnglish
Pages (from-to)947-956
Number of pages10
JournalCarcinogenesis
Volume28
Issue number5
DOIs
StatePublished - 1 May 2007

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IGF Type 1 Receptor
Somatomedins
Insulin-Like Growth Factor II
Therapeutics
Neoplasms
Ligands
Somatomedin Receptors
Esophageal Squamous Cell Carcinoma
Recurrence
Therapeutic Uses
Multivariate Analysis
Apoptosis
Neoplasm Metastasis
Survival

Cite this

Imsumran, Arisa ; Adachi, Yasushi ; Yamamoto, Hiroyuki ; Li, Rong ; Wang, Yu ; Min, Yongfen ; Piao, Wenhua ; Nosho, Katsuhiko ; Arimura, Yoshiaki ; Shinomura, Yasuhisa ; Hosokawa, Masao ; Lee, Choon Taek ; Carbone, David P. ; Imai, Kohzoh. / Insulin-like growth factor-I receptor as a marker for prognosis and a therapeutic target in human esophageal squamous cell carcinoma. In: Carcinogenesis. 2007 ; Vol. 28, No. 5. pp. 947-956.
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title = "Insulin-like growth factor-I receptor as a marker for prognosis and a therapeutic target in human esophageal squamous cell carcinoma",
abstract = "Insulin-like growth factor (IGF)-I receptor (IGF-Ir) signaling is required for tumorigenicity and progression of many tumors but this pathway has not been well studied as a prognostic factor or potential therapeutic target in esophageal squamous cell carcinoma (ESCC). In this paper, the association between the expression of IGF-Ir and IGF-II ligand and prognosis was investigated immunohistochemically in 100 surgically resected ESCC.We then assessed the therapeutic effect of blocking IGF receptor signaling using dominant negative IGF-Ir (IGF-Ir/ dn) in ESCC in vitro. Expression of IGF-Ir and IGF-II were detected in 60 and 50{\%} of tumors, respectively, and were associated with invasion depth, metastasis, advanced tumor stage and recurrence. Patients with tumors expressing both IGF-Ir and IGF-II had a significantly shorter survival than those expressing either alone or neither in both single and multivariate analysis. IGF-Ir/dn suppressed proliferation and motility as well as upregulating chemotherapyinduced apoptosis through blocking ligand-induced Akt activation. We propose that detection of IGF-Ir/IGF-II in ESCC may be useful for the prediction of recurrence and poor prognosis and for selecting patients for IGF-Ir-targeted therapy. Therapeutic blockade of IGF-Ir may be a useful anticancer therapeutic for ESCC.",
author = "Arisa Imsumran and Yasushi Adachi and Hiroyuki Yamamoto and Rong Li and Yu Wang and Yongfen Min and Wenhua Piao and Katsuhiko Nosho and Yoshiaki Arimura and Yasuhisa Shinomura and Masao Hosokawa and Lee, {Choon Taek} and Carbone, {David P.} and Kohzoh Imai",
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Imsumran, A, Adachi, Y, Yamamoto, H, Li, R, Wang, Y, Min, Y, Piao, W, Nosho, K, Arimura, Y, Shinomura, Y, Hosokawa, M, Lee, CT, Carbone, DP & Imai, K 2007, 'Insulin-like growth factor-I receptor as a marker for prognosis and a therapeutic target in human esophageal squamous cell carcinoma', Carcinogenesis, vol. 28, no. 5, pp. 947-956. https://doi.org/10.1093/carcin/bgl247

Insulin-like growth factor-I receptor as a marker for prognosis and a therapeutic target in human esophageal squamous cell carcinoma. / Imsumran, Arisa; Adachi, Yasushi; Yamamoto, Hiroyuki; Li, Rong; Wang, Yu; Min, Yongfen; Piao, Wenhua; Nosho, Katsuhiko; Arimura, Yoshiaki; Shinomura, Yasuhisa; Hosokawa, Masao; Lee, Choon Taek; Carbone, David P.; Imai, Kohzoh.

In: Carcinogenesis, Vol. 28, No. 5, 01.05.2007, p. 947-956.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Insulin-like growth factor-I receptor as a marker for prognosis and a therapeutic target in human esophageal squamous cell carcinoma

AU - Imsumran, Arisa

AU - Adachi, Yasushi

AU - Yamamoto, Hiroyuki

AU - Li, Rong

AU - Wang, Yu

AU - Min, Yongfen

AU - Piao, Wenhua

AU - Nosho, Katsuhiko

AU - Arimura, Yoshiaki

AU - Shinomura, Yasuhisa

AU - Hosokawa, Masao

AU - Lee, Choon Taek

AU - Carbone, David P.

AU - Imai, Kohzoh

PY - 2007/5/1

Y1 - 2007/5/1

N2 - Insulin-like growth factor (IGF)-I receptor (IGF-Ir) signaling is required for tumorigenicity and progression of many tumors but this pathway has not been well studied as a prognostic factor or potential therapeutic target in esophageal squamous cell carcinoma (ESCC). In this paper, the association between the expression of IGF-Ir and IGF-II ligand and prognosis was investigated immunohistochemically in 100 surgically resected ESCC.We then assessed the therapeutic effect of blocking IGF receptor signaling using dominant negative IGF-Ir (IGF-Ir/ dn) in ESCC in vitro. Expression of IGF-Ir and IGF-II were detected in 60 and 50% of tumors, respectively, and were associated with invasion depth, metastasis, advanced tumor stage and recurrence. Patients with tumors expressing both IGF-Ir and IGF-II had a significantly shorter survival than those expressing either alone or neither in both single and multivariate analysis. IGF-Ir/dn suppressed proliferation and motility as well as upregulating chemotherapyinduced apoptosis through blocking ligand-induced Akt activation. We propose that detection of IGF-Ir/IGF-II in ESCC may be useful for the prediction of recurrence and poor prognosis and for selecting patients for IGF-Ir-targeted therapy. Therapeutic blockade of IGF-Ir may be a useful anticancer therapeutic for ESCC.

AB - Insulin-like growth factor (IGF)-I receptor (IGF-Ir) signaling is required for tumorigenicity and progression of many tumors but this pathway has not been well studied as a prognostic factor or potential therapeutic target in esophageal squamous cell carcinoma (ESCC). In this paper, the association between the expression of IGF-Ir and IGF-II ligand and prognosis was investigated immunohistochemically in 100 surgically resected ESCC.We then assessed the therapeutic effect of blocking IGF receptor signaling using dominant negative IGF-Ir (IGF-Ir/ dn) in ESCC in vitro. Expression of IGF-Ir and IGF-II were detected in 60 and 50% of tumors, respectively, and were associated with invasion depth, metastasis, advanced tumor stage and recurrence. Patients with tumors expressing both IGF-Ir and IGF-II had a significantly shorter survival than those expressing either alone or neither in both single and multivariate analysis. IGF-Ir/dn suppressed proliferation and motility as well as upregulating chemotherapyinduced apoptosis through blocking ligand-induced Akt activation. We propose that detection of IGF-Ir/IGF-II in ESCC may be useful for the prediction of recurrence and poor prognosis and for selecting patients for IGF-Ir-targeted therapy. Therapeutic blockade of IGF-Ir may be a useful anticancer therapeutic for ESCC.

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U2 - 10.1093/carcin/bgl247

DO - 10.1093/carcin/bgl247

M3 - Article

C2 - 17183068

AN - SCOPUS:34447095442

VL - 28

SP - 947

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JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

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