Anti-progranulin/GP88 antibody AG01 inhibits triple negative breast cancer cell proliferation and migration.
Anti-progranulin/GP88 antibody AG01 inhibits triple negative breast cancer cell proliferation and migration.
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DOI：
10.1007/s10549-021-06120-y
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发表时间：
2021-04
影响因子：
3.8
通讯作者：
Serrero G
中科院分区：
文献类型：
--
作者：
Guha R;Yue B;Dong J;Banerjee A;Serrero G
三阴性乳腺癌（TNBC）的特征是侵袭性和短生存期。鉴定新的TNBC靶向疗法以加强护理标准（SOC）疗法是未满足的需求。颗粒蛋白前体（PGRN/GP 88）是包括乳腺癌（BC）在内的几种癌症中肿瘤发生、存活和耐药性的生物驱动因素。PGRN/GP 88组织表达是复发的独立预后因素，而血清PGRN/GP 88水平升高与不良预后相关。由于PGRN/GP 88表达在30%TNBC中升高，我们研究了颗粒蛋白前体对TNBC的参与。研究通过siRNA抑制TNBC细胞中PGRN/GP 88表达的效果。然后在体外和体内检查中和抗人PGRN/GP 88单克隆抗体AG 01对表达PGRN/GP 88的两种TNBC细胞系的增殖和迁移的影响。通过siRNA抑制GP 88表达和AG 01处理阻断PGRN/GP 88作用以剂量依赖性方式降低MDA-MB-231和HS 578-T细胞的增殖和迁移。Western印迹分析显示，AG 01处理后磷酸化蛋白激酶p-Src、p-AKT和p-ERK的表达降低，以及体内肿瘤生长和Ki 67表达的抑制。PGRN/GP 88代表具有伴随诊断的治疗靶标。用抗体治疗阻断PGRN/GP 88可以在TNBC治疗中提供新的靶向解决方案，其可以最终解决与SOC相关的毒性和无反应性的问题。
Triple negative breast cancer (TNBC) is characterized by invasiveness and short survival. Identifying novel TNBC-targeted therapies, to potentiate standard of care (SOC) therapy, is an unmet need. Progranulin (PGRN/GP88) is a biological driver of tumorigenesis, survival, and drug resistance in several cancers including breast cancer (BC). PGRN/GP88 tissue expression is an independent prognostic factor of recurrence while elevated serum PGRN/GP88 level is associated with poor outcomes. Since PGRN/GP88 expression is elevated in 30% TNBC, we investigated the involvement of progranulin on TNBC. The effect of inhibiting PGRN/GP88 expression in TNBC cells by siRNA was investigated. The effects of a neutralizing anti-human PGRN/GP88 monoclonal antibody AG01 on the proliferation and migration of two TNBC cell lines expressing PGRN/GP88 were then examined in vitro and in vivo. Inhibition of GP88 expression by siRNA and AG01 treatment to block PGRN/GP88 action reduced proliferation and migration in a dose-dependent fashion in MDA-MB-231 and HS578-T cells. Western blot analysis showed decreased expression of phosphorylated protein kinases p-Src, p-AKT, and p-ERK upon AG01 treatment, as well as inhibition of tumor growth and Ki67 expression in vivo. PGRN/GP88 represents a therapeutic target with companion diagnostics. Blocking PGRN/GP88 with antibody treatment may provide novel-targeted solutions in TNBC treatment which could eventually address the issue of toxicity and unresponsiveness associated with SOC.
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影响因子：
3.6
作者：
Dong, Taotao;Yang, Dong;Wang, Linlin
通讯作者：
Wang, Linlin
影响因子：
15.9
作者：
Elkabets, Moshe;Gifford, Ann M.;McAllister, Sandra S.
通讯作者：
McAllister, Sandra S.
影响因子：
50.5
作者：
Gonzalez-Angulo, A. M.;Akcakanat, A.;Meric-Bernstam, F.
通讯作者：
Meric-Bernstam, F.
DOI：
10.1038/nrn.2017.36
发表时间：
2017-06
期刊：
Nature reviews. Neuroscience
影响因子：
--
作者：
Kao AW;McKay A;Singh PP;Brunet A;Huang EJ
通讯作者：
Huang EJ
DOI：
10.1007/s12032-017-1054-7
发表时间：
2017-11-07
期刊：
Medical oncology (Northwood, London, England)
影响因子：
--
作者：
Arechavaleta-Velasco F;Perez-Juarez CE;Gerton GL;Diaz-Cueto L
通讯作者：
Diaz-Cueto L