Processing of syndecan-2 by matrix metalloproteinase-14 and effect of its cleavage on VEGF-induced tube formation of HUVECs

Young Hun Lee, Jun Hyoung Park, Dong Huey Cheon, Taeyoung Kim, Yae Eun Park, Eok Soo Oh, Ji Eun Lee, Seung-Taek Lee

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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 S88↓L89, T98↓M99, T100↓L101, D132↓P133, and N148↓L149 for rat SDC2-ECD and S55↓G56, S65↓P66, P75↓K76, N92↓I93 D122↓P123, and S138↓L139 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.

Original languageEnglish
Pages (from-to)3719-3732
Number of pages14
JournalBiochemical Journal
Volume474
Issue number22
DOIs
Publication statusPublished - 2017 Nov 15

Fingerprint

Syndecan-2
Matrix Metalloproteinase 14
Matrix Metalloproteinases
Vascular Endothelial Growth Factor A
Rats
Matrix Metalloproteinase 7
Processing
Syndecans
Cells
Protein Sequence Analysis
Human Umbilical Vein Endothelial Cells
Proteoglycans
HeLa Cells
Cell adhesion
Endothelial cells
Cell Adhesion
Cell Communication
Proteomics
Colonic Neoplasms
Carcinogenesis

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lee, Young Hun ; Park, Jun Hyoung ; Cheon, Dong Huey ; Kim, Taeyoung ; Park, Yae Eun ; Oh, Eok Soo ; Lee, Ji Eun ; Lee, Seung-Taek. / Processing of syndecan-2 by matrix metalloproteinase-14 and effect of its cleavage on VEGF-induced tube formation of HUVECs. In: Biochemical Journal. 2017 ; Vol. 474, No. 22. pp. 3719-3732.
@article{13d2c9dedfac416c80d708367a48d579,
title = "Processing of syndecan-2 by matrix metalloproteinase-14 and effect of its cleavage on VEGF-induced tube formation of HUVECs",
abstract = "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 S88↓L89, T98↓M99, T100↓L101, D132↓P133, and N148↓L149 for rat SDC2-ECD and S55↓G56, S65↓P66, P75↓K76, N92↓I93 D122↓P123, and S138↓L139 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.",
author = "Lee, {Young Hun} and Park, {Jun Hyoung} and Cheon, {Dong Huey} and Taeyoung Kim and Park, {Yae Eun} and Oh, {Eok Soo} and Lee, {Ji Eun} and Seung-Taek Lee",
year = "2017",
month = "11",
day = "15",
doi = "10.1042/BCJ20170340",
language = "English",
volume = "474",
pages = "3719--3732",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "22",

}

Processing of syndecan-2 by matrix metalloproteinase-14 and effect of its cleavage on VEGF-induced tube formation of HUVECs. / Lee, Young Hun; Park, Jun Hyoung; Cheon, Dong Huey; Kim, Taeyoung; Park, Yae Eun; Oh, Eok Soo; Lee, Ji Eun; Lee, Seung-Taek.

In: Biochemical Journal, Vol. 474, No. 22, 15.11.2017, p. 3719-3732.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Processing of syndecan-2 by matrix metalloproteinase-14 and effect of its cleavage on VEGF-induced tube formation of HUVECs

AU - Lee, Young Hun

AU - Park, Jun Hyoung

AU - Cheon, Dong Huey

AU - Kim, Taeyoung

AU - Park, Yae Eun

AU - Oh, Eok Soo

AU - Lee, Ji Eun

AU - Lee, Seung-Taek

PY - 2017/11/15

Y1 - 2017/11/15

N2 - 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 S88↓L89, T98↓M99, T100↓L101, D132↓P133, and N148↓L149 for rat SDC2-ECD and S55↓G56, S65↓P66, P75↓K76, N92↓I93 D122↓P123, and S138↓L139 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.

AB - 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 S88↓L89, T98↓M99, T100↓L101, D132↓P133, and N148↓L149 for rat SDC2-ECD and S55↓G56, S65↓P66, P75↓K76, N92↓I93 D122↓P123, and S138↓L139 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.

UR - http://www.scopus.com/inward/record.url?scp=85033379773&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85033379773&partnerID=8YFLogxK

U2 - 10.1042/BCJ20170340

DO - 10.1042/BCJ20170340

M3 - Article

C2 - 28972070

AN - SCOPUS:85033379773

VL - 474

SP - 3719

EP - 3732

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 22

ER -