Lee, Young Hun Park, Jun Hyoung Cheon, Dong Huey Kim, Taeyoung Park, Yae Eun Oh, Eok-Soo Lee, Ji Eun Lee, Seung-Taek 2024-01-20T00:03:13Z 2024-01-20T00:03:13Z 2021-09-03 2017-11-15 0264-6021 https://pubs.kist.re.kr/handle/201004/122056 Syndecans (SDCs) are transmembrane proteoglycans that are involved in cell adhesion and cell communication. Specifically, SDC2 plays a key role in tumorigenesis, metastasis, and angiogenesis. Previously, we found that rat SDC2 is shed by matrix metalloproteinase- 7 (MMP-7) in colon cancer cells. Here, we analyzed the susceptibility of rat SDC2 to various MMPs. We found that the rat SDC2 ectodomain (ECD) fused to the C-terminal Fc region, which was expressed in mammalian cells, was cleaved more efficiently by MMP-14 than MMP-7. Likewise, when anchored on the surface of HeLa cells, rat SDC2 was cleaved more efficiently by the treatment of MMP-14 than MMP-7 and was shed more readily by membrane-anchored MMP-14 than soluble MMP-14. Furthermore, MMP-14 cleaved recombinant SDC2-ECD expressed in Escherichia coli into multiple fragments. Using N-terminal amino acid sequencing and the top-down proteomics approach, we determined that the major cleavage sites were S-88 down arrow L-89, T-98 down arrow M-99, T-100 down arrow L-101, D-132 down arrow P-133, and N-148 down arrow L-149 for rat SDC2-ECD and S-55 down arrow G(56), S-65 down arrow P-66, P-75 down arrow K-76, N-92 down arrow I-93 D-122 down arrow P-123, and S-138 down arrow L-139 for human SDC2-ECD. Finally, the rat and human SDC2-ECD lost the ability to suppress vascular endothelial growth factor-induced formation of capillary-like tubes by human umbilical vein endothelial cells following cleavage by MMP-14, but its major cleavage-site mutant of rat SDC2-ECD did not. These results suggest that MMP-14 is a novel enzyme responsible for degrading SDC2 and impairing its physiological roles including angiogenesis. English PORTLAND PRESS LTD MICROVASCULAR ENDOTHELIAL-CELLS COLON-CARCINOMA CELLS COLORECTAL-CANCER TISSUE INHIBITOR ANGIOGENESIS ACTIVATION EXPRESSION SUBSTRATE PROTEOGLYCAN DISEASE Processing of syndecan-2 by matrix metalloproteinase-14 and effect of its cleavage on VEGF-induced tube formation of HUVECs Article 10.1042/BCJ20170340 1 BIOCHEMICAL JOURNAL, v.474, pp.3719 - 3732 BIOCHEMICAL JOURNAL 474 3719 3732 scie scopus 000415328400002 2-s2.0-85033379773 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article MICROVASCULAR ENDOTHELIAL-CELLS COLON-CARCINOMA CELLS COLORECTAL-CANCER TISSUE INHIBITOR ANGIOGENESIS ACTIVATION EXPRESSION SUBSTRATE PROTEOGLYCAN DISEASE