Novel antibodies against GPIbα inhibit pulmonary metastasis by affecting vWF-GPIbα interaction.
Novel antibodies against GPIbα inhibit pulmonary metastasis by affecting vWF-GPIbα interaction.
复制标题
针对 GPIb α 的新型抗体通过影响 vWF-GPIb α 相互作用抑制肺转移
DOI：
10.1186/s13045-018-0659-4
复制
发表时间：
2018-09-17
影响因子：
28.5
通讯作者：
Liang X
中科院分区：
文献类型：
--
作者：
Qi Y;Chen W;Liang X;Xu K;Gu X;Wu F;Fan X;Ren S;Liu J;Zhang J;Li R;Liu J;Liang X
血小板糖蛋白Ibα（GPIbα）胞外区是GPIb-IX-V受体复合物的一部分，在肿瘤转移中起重要作用。然而，GPIbα参与转移过程的机制仍不清楚。此外，潜在的出血并发症仍然是抗血小板药物在癌症治疗中临床应用的障碍。我们建立了一系列的筛选模型，获得了大鼠抗小鼠GPIbα单克隆抗体（mAb）1D 12和2B 4。为了验证我们的发现，我们进一步通过同样的方法获得了鼠抗人GPIbα单克隆抗体YQ 3。1D 12和2B 4分别通过与GPIbα aa 41-50和aa 277-290结合，影响vWF-GPIbα相互作用，在体外显著抑制血小板、肿瘤细胞和内皮细胞之间的相互作用，在体内实验和自发转移模型中显著减少表面结节的平均数目。正如预期的那样，YQ 3抑制肺癌粘附，并在转移中表现出类似的价值。更重要的是，对于我们研究中的所有三种mAb，它们的Fab均不诱导血小板减少症。本研究结果支持了GPIbα参与肿瘤转移的假说，并提示了抗GPIb α单克隆抗体对抑制肿瘤转移的潜在价值。本文的在线版本（10.1186/s13045-018-0659-4）包含补充材料，可供授权用户使用。
Platelet glycoprotein Ibα (GPIbα) extracellular domain, which is part of the receptor complex GPIb-IX-V, plays an important role in tumor metastasis. However, the mechanism through which GPIbα participates in the metastatic process remains unclear. In addition, potential bleeding complication remains an obstacle for the clinical use of anti-platelet agents in cancer therapy. We established a series of screening models and obtained rat anti-mouse GPIbα monoclonal antibodies (mAb) 1D12 and 2B4 that demonstrated potential value in suppressing cancer metastasis. To validate our findings, we further obtained mouse anti-human GPIbα monoclonal antibody YQ3 through the same approach. 1D12 and 2B4 affected the von Willebrand factor (vWF)-GPIbα interaction via binding to GPIbα aa 41-50 and aa 277-290 respectively, which markedly inhibited the interaction among platelets, tumor cells, and endothelial cells in vitro, and reduced the mean number of surface nodules in the experimental and spontaneous metastasis models in vivo. As expected, YQ3 inhibited lung cancer adhesion and demonstrated similar value in metastasis. More importantly, for all three mAbs in our study, none of their Fabs induced thrombocytopenia. Our results therefore supported the hypothesis that GPIbα contributes to tumor metastasis and suggested potential value of using anti-GPIbα mAb to suppress cancer metastasis. The online version of this article (10.1186/s13045-018-0659-4) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
4.7
作者：
Gucer, F;Moser, F;Winter, R
通讯作者：
Winter, R
影响因子：
15.9
作者：
Nardi, M;Feinmark, SJ;Karpatkin, S
通讯作者：
Karpatkin, S
影响因子：
15.9
作者：
Li, Conglei;Piran, Siavash;Ni, Heyu
通讯作者：
Ni, Heyu
影响因子：
6.5
作者：
Erpenbeck, Luise;Nieswandt, Bernhard;Schoen, Michael P.
通讯作者：
Schoen, Michael P.
DOI：
10.1111/jth.12425
发表时间：
2013-12
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Liang X;Russell SR;Estelle S;Jones LH;Cho S;Kahn ML;Berndt MC;Bunting ST;Ware J;Li R
通讯作者：
Li R