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整合素α10抗体可减少胶质母细胞瘤的肿瘤生长和细胞迁移。

Integrin α10-Antibodies Reduce Glioblastoma Tumor Growth and Cell Migration.

作者信息

Masoumi Katarzyna Chmielarska, Huang Xiaoli, Sime Wondossen, Mirkov Anna, Munksgaard Thorén Matilda, Massoumi Ramin, Lundgren-Åkerlund Evy

机构信息

Xintela AB, Medicon Village, Scheeletorget 1, SE-223 81 Lund, Sweden.

IVRS AB, Medicon Village, Scheeletorget 1, SE-223 81 Lund, Sweden.

出版信息

Cancers (Basel). 2021 Mar 9;13(5):1184. doi: 10.3390/cancers13051184.

Abstract

Glioblastoma (GB) is the most common and the most aggressive form of brain tumor in adults, which currently lacks efficient treatment strategies. In this study, we investigated the therapeutic effect of function-blocking antibodies targeting integrin α10β1 on patient-derived-GB cell lines in vitro and in vivo. The in vitro studies demonstrated significant inhibiting effects of the integrin α10 antibodies on the adhesion, migration, proliferation, and sphere formation of GB cells. In a xenograft mouse model, the effect of the antibodies on tumor growth was investigated in luciferase-labeled and subcutaneously implanted GB cells. As demonstrated by in vivo imaging analysis and caliper measurements, the integrin α10-antibodies significantly suppressed GB tumor growth compared to control antibodies. Immunohistochemical analysis of the GB tumors showed lower expression of the proliferation marker Ki67 and an increased expression of cleaved caspase-3 after treatment with integrin α10 antibodies, further supporting a therapeutic effect. Our results suggest that function-blocking antibody targeting integrin α10β1 is a promising therapeutic strategy for the treatment of glioblastoma.

摘要

胶质母细胞瘤(GB)是成人中最常见且侵袭性最强的脑肿瘤形式,目前缺乏有效的治疗策略。在本研究中,我们调查了靶向整合素α10β1的功能阻断抗体对源自患者的GB细胞系的体内外治疗效果。体外研究表明,整合素α10抗体对GB细胞的黏附、迁移、增殖和球体形成具有显著抑制作用。在异种移植小鼠模型中,在荧光素酶标记并皮下植入的GB细胞中研究了抗体对肿瘤生长的影响。如体内成像分析和卡尺测量所示,与对照抗体相比,整合素α10抗体显著抑制了GB肿瘤生长。GB肿瘤的免疫组织化学分析显示,用整合素α10抗体治疗后,增殖标志物Ki67的表达降低,而裂解的半胱天冬酶-3的表达增加,进一步支持了治疗效果。我们的结果表明,靶向整合素α10β1的功能阻断抗体是治疗胶质母细胞瘤的一种有前景的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5b6/7980568/7b6d0a8f35f7/cancers-13-01184-g001.jpg

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