Novel antibodies against GPIb? inhibit pulmonary metastasis by affecting vWF-GPIb? interaction.

ABSTRACT: BACKGROUND:Platelet glycoprotein Ib? (GPIb?) extracellular domain, which is part of the receptor complex GPIb-IX-V, plays an important role in tumor metastasis. However, the mechanism through which GPIb? 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. METHODS:We established a series of screening models and obtained rat anti-mouse GPIb? monoclonal antibodies (mAb) 1D12 and 2B4 that demonstrated potential value in suppressing cancer metastasis. To validate our findings, we further obtained mouse anti-human GPIb? monoclonal antibody YQ3 through the same approach. RESULTS:1D12 and 2B4 affected the von Willebrand factor (vWF)-GPIb? interaction via binding to GPIb? 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. CONCLUSION:Our results therefore supported the hypothesis that GPIb? contributes to tumor metastasis and suggested potential value of using anti-GPIb? mAb to suppress cancer metastasis.

SUBMITTER: Qi Y 

PROVIDER: S-EPMC6142402 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature