View : 18 Download: 5

MMP9 Processing of HSPB1 Regulates Tumor Progression

Title
MMP9 Processing of HSPB1 Regulates Tumor Progression
Authors
Choi, Seo-hyunLee, Hae-JuneJin, Yeung BaeJang, JunhoKang, Ga-YoungLee, MinyoungKim, Chun-HoKim, JoonYoon, Sam S.Lee, Yun-SilLee, Yoon-Jin
Ewha Authors
이윤실
SCOPUS Author ID
이윤실scopus
Issue Date
2014
Journal Title
PLOS ONE
ISSN
1932-6203JCR Link
Citation
vol. 9, no. 1
Publisher
PUBLIC LIBRARY SCIENCE
Indexed
SCIE; SCOPUS WOS
Abstract
Matrix metalloproteinases regulate pathophysiological events by processing matrix proteins and secreted proteins. Previously, we demonstrated that soluble heat shock protein B1 (HSPB1) is released primarily from endothelial cells (ECs) and regulates angiogenesis via direct interaction with vascular endothelial growth factor (VEGF). Here we report that MMP9 can cleave HSPB1 and release anti-angiogenic fragments, which play a key role in tumorprogression. We mapped the cleavage sites and explored their physiological relevance during these processing events. HSPB1 cleavage by MMP9 inhibited VEGF-induced ECs activation and the C-terminal HSPB1 fragment exhibited more interaction with VEGF than did full-length HSPB1. HSPB1 cleavage occurs during B16F10 lung progression in wild-type mice. Also, intact HSPB1 was more detected on tumor endothelium of MMP9 null mice than wild type mice. Finally, we confirmed that secretion of C-terminal HSPB1 fragment was significantly inhibited lung and liver tumor progression of B16F10 melanoma cells and lung tumor progression of CT26 colon carcinoma cells, compared to full-length HSPB1. These data suggest that in vivo MMP9-mediated processing of HSPB1 acts to regulate VEGF-induced ECs activation for tumor progression, releasing anti-angiogenic HSPB1 fragments. Moreover, these findings potentially explain an anti-target effect for the failure of MMP inhibitors in clinical trials, suggesting that MMP inhibitors may have pro-tumorigenic effects by reducing HSPB1 fragmentation.
DOI
10.1371/journal.pone.0085509
Appears in Collections:
약학대학 > 약학과 > Journal papers
Files in This Item:
001.pdf(2.27 MB)Download
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE