The matrix metalloproteinase-7 regulates the extracellular shedding of syndecan-2 from colon cancer cells.
The cell surface heparan sulfate proteoglycan syndecan-2 regulates the activation of matrix metalloproteinase-7 (MMP-7) as a docking receptor. Here, we demonstrate the role of MMP-7 on syndecan-2 shedding in colon cancer cells. Western blot analysis showed that shed syndecan-2 was found in the culture media from various colon cancer cells. Overexpression of MMP-7 enhanced syndecan-2 shedding, whereas the opposite was true when MMP-7 levels were knocked-down using small inhibitory RNAs. Consistently, HT29 cells treated with MMP-7, but neither MMP-2 nor MMP-9, showed increased shed syndecan-2 in a time- and concentration-dependent manner. Furthermore, MALDI-TOF MS analysis and N-terminal amino acid sequencing revealed that MMP-7 cleaved both recombinant syndecan-2 and an endogenously glycosylated syndecan-2 ectodomain in the N-terminus at Leu(149) residue in vitro. Taken together, the data suggest that MMP-7 directly mediates shedding of syndecan-2 from colon cancer cells.
Department of Life Sciences, Division of Life and Pharmaceutical Sciences, The Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, Seoul 120-750, Republic of Korea.
Sojoong
S
Choi
Jin-Yung
JY
Kim
Jun Hyoung
JH
Park
Seung-Teak
ST
Lee
Inn-Oc
IO
Han
Eok-Soo
ES
Oh
D003110:Colonic Neoplasms / Q000378:metabolism*; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D053669:Syndecan-2 / Q000378:metabolism*; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D053669:Syndecan-2; C094027:TRIM32 protein, human; D044767:Ubiquitin-Protein Ligases; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7