Insulin-like growth factor-I receptor as a marker for prognosis and a therapeutic target in human esophageal squamous cell carcinoma.
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 chemotherapy-induced 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.
Imsumran
Arisa
A
First Department of Internal Medicine, Sapporo Medical University, South-1, West-16, Chuo-ku, Sapporo 060-8543, Japan.
Adachi
Yasushi
Y
Yamamoto
Hiroyuki
H
Li
Rong
R
Wang
Yu
Y
Min
Yongfen
Y
Piao
Wenhua
W
Nosho
Katsuhiko
K
Arimura
Yoshiaki
Y
Shinomura
Yasuhisa
Y
Hosokawa
Masao
M
Lee
Choon-Taek
CT
Carbone
David P
DP
Imai
Kohzoh
K
D000256:Adenoviridae / Q000235:genetics; D000368:Aged; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000628:therapy*; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000628:therapy*; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D017526:Receptor, IGF Type 1 / Q000819:agonists* / Q000032:analysis*; D016019:Survival Analysis; D014162:Transfection
D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1