Development of a novel therapeutic approach targeting the processing of angiopoietin-like protein 2 for suppressing of tumor metastasis

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K20008
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Kumamoto University (2016); Teikyo University (2015)
• Principal Investigator: Odagiri Haruki 熊本大学, 生命資源研究・支援センター, 客員助教 (60732740)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: がん / ANGPTL2 / プロセシング

Outline of Final Research Achievements

Here, we show that TLL1 (tolloid-like 1) predominantly contributes to the processing of ANGPTL2 among BMP-1 (bone morphogenic protein-1)/TLD (tolloid) family proteins. In addition, we found that secreted ANGPTL2 proteins are O-glycosylated in the conditioned medium of human tumor cell lines. We also identified an O-glycosylation site of ANGPTL2 protein and showed that ANGPTL2 proteins containing the mutated O-glycosylation site exhibit increased susceptibility to cleavage by TLL1. These results suggest that O-glycosylation of ANGPTL2 protein is important for protection from cleavage by TLL1. Therefore, not only promoting the activity and expression of TLL1, but also suppressing the O-glycosylation of ANGPTL2 protein in tumor cells may be a novel therapeutic approach for ANGPTL2 signaling-mediated tumor metastasis.

Free Research Field

腫瘍生物学