Background: Platelet glycoprotein Iba (GPIb alpha) 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 alpha 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 alpha 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 alpha monoclonal antibody YQ3 through the same approach.
Results: 1D12 and 2B4 affected the von Willebrand factor (vWF)-GPIb alpha interaction via binding to GPIb alpha 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 alpha contributes to tumor metastasis and suggested potential value of using anti-GPIb alpha mAb to suppress cancer metastasis.
[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Sch Pharm, 130 Meilong Rd, Shanghai 200237, Peoples R China.
[2]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, 130 Meilong Rd, Shanghai 200237, Peoples R China.
[3]Emory Univ, Sch Med, Dept Pediat, Aflac Canc & Blood Disorders Ctr,Childrens Health, Atlanta, GA 30322 USA.
[4]Shanghai Univ Tradit Chinese Med, Cent Lab, Gen Surg, Putuo Hosp, 164 Lanxi Rd, Shanghai 200062, Peoples R China.
[5]Shanghai Univ Tradit Chinese Med, Intervent Canc Inst Chinese Integrat Med, 164 Lanxi Rd, Shanghai 200062, Peoples R China.
[6]Tongji Univ, Dept Med Oncol, Shanghai Pulm Hosp, Thorac Canc Inst,Sch Med, Shanghai, Peoples R China.
[7]Shanghai Jiao Tong Univ, Dept Biochem & Mol Cell Biol, Shanghai Key Lab Tumor Microenvironm & Inflammat, Sch Med, Shanghai 200025, Peoples R China.
[8]Univ Iowa, Dept Internal Med, Div Hematol Oncol & Blood & Marrow Transplantat, Holden Comprehens Canc Ctr,Carver Coll Med, Iowa City, IA 52242 USA.
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