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抗体靶向 ADAMTS1 抑制乳腺癌在小鼠异种移植瘤中的生长。

Inhibition of tumor growth by antibody to ADAMTS1 in mouse xenografts of breast cancer.

机构信息

Division of Breast and Endocrine Surgery, Department of Surgery, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan.

出版信息

Anticancer Res. 2011 Nov;31(11):3839-42.

Abstract

BACKGROUND

A disintegrin and metalloproteinase with thrombospondin motifs-1 (ADAMTS1), a member of the ADAMTS family of proteases, is involved in the shedding of epidermal growth factor (EGF)-like ligands such as amphiregulin, which activate the EGF receptor. Since ADAMTS1 has been implicated in aggressive breast carcinogenesis, we examined potential antitumor effects of antibody to ADAMTS1 in a mouse model of breast cancer.

MATERIALS AND METHODS

BALB/c female mice were inoculated with syngenic 4T1 breast cancer cells and treated with anti-ADAMTS1 antibody or control IgG. Tumor volume and weight were evaluated.

RESULTS

Mouse 4T1 cells expressed ADAMTS1 and its substrates amphiregulin and heparin-binding EGF. Treatment with antibody to ADAMTS1 inhibited tumor growth without any adverse effects.

CONCLUSION

ADAMTS1 could be a promising molecular target for immunotherapy of breast cancer.

摘要

背景

解整合素金属蛋白酶 13(ADAMTS1)是 ADAMTS 蛋白酶家族的成员,参与表皮生长因子(EGF)样配体如 Amphiregulin 的脱落,这些配体激活 EGF 受体。由于 ADAMTS1 与侵袭性乳腺癌的发生有关,我们在乳腺癌小鼠模型中研究了抗 ADAMTS1 抗体的潜在抗肿瘤作用。

材料与方法

BALB/c 雌性小鼠接种同源 4T1 乳腺癌细胞,并接受抗 ADAMTS1 抗体或对照 IgG 治疗。评估肿瘤体积和重量。

结果

小鼠 4T1 细胞表达 ADAMTS1 及其底物 Amphiregulin 和肝素结合 EGF。用抗 ADAMTS1 抗体治疗可抑制肿瘤生长,无任何不良反应。

结论

ADAMTS1 可能成为乳腺癌免疫治疗的有前途的分子靶点。

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