Inhibition of breast cancer cell proliferation and migration by monoclonal antibody m590 specific for insulin-like growth factor receptor type I

Abstract

Objective To investigate the mechanism(s) that a human-mouse chimeric monoclonal anti-insulin-like growth factor receptor type Ⅰ (IGF-IR) antibody,m590,inhibits breast cancer cells proliferation and migration.Methods Binding of m590 to IGF-IR in 30 breast cancer samples was detected by using immunohistochemistry.Western blotting,immunocytofluorescence and other tests were used for analyzing the effects of m590 on breast cancer cells ( MCF-7 ) proliferation,survival,adhesion and migration as well as signaling pathways.Results m590 specifically bound to IGF-IR was overexpressed in invasive ductal carcinoma of the breast (87％ of cases).Treatment of MCF-7 cells with m590 significantly suppressed IGF-I-induced phosphorylation of ERK and Akt,which led to reduced cell proliferation by 58％and increased apoptosis.m590 also inhibited IGF-Ⅰ-induced polymerization of F-actin and relocation of vinculin in cell edge,resulting in dramatically decreased cell migration by 56％ and cell adhesion by 55％.Furthermore,herceptin in combination with m590 synergistically inhibited IGF-IR-induced phosphorylation of ERK and AKT,and decreased MCF-7 cells proliferation by 76％ as compared with IGF-I treatment alone.Conclusion m590 is an effective anti-IGF-IR antibody and may have the potential in clinical use for diagnosis and treatment of breast cancer.

目的探討抗胰島素樣生長因子Ⅰ型受體(IGF-IR)抗體,m590,抑制乳腺癌細胞增生、遷移及其機制.方法免疫組織化學染色30例乳腺浸潤性導管癌標本；免疫印跡法、免疫熒光細胞染色及其他試驗檢測m590 對MCF-7細胞的作用及其機制.結果87％的乳腺浸潤性導管癌高表達IGF-IR；m590抑制胰島素樣生長因子Ⅰ(IGF-I)誘導的細胞外調節蛋白激酶(ERK)和蛋白激酶B(Akt)磷酸化以及細胞骨架蛋白(F-actin)和細胞骨架黏合班蛋白(Vinculin)在細胞內的分佈,使細胞增生、遷移和黏附分別降低至5​​8 ％、56％和55％,並促進細胞凋亡；M590 與赫賽汀聯用抑制IGF-I誘導的ERK和Akt 磷酸化,使細胞增生降低76％.結論m590 是一個有效抑制乳腺癌細胞增生、遷移和黏附的抗IGF-IR抗體.