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

Research Project

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
Project Status	Completed (Fiscal Year 2016)
Budget Amount *help	¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000) Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords	がん / ANGPTL2 / プロセシング / TLL1 / 低分子化合物 / がん抑制遺伝子
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.