Clusterin induces matrix metalloproteinase-9 expression via ERK1/2 and PI3K/Akt/NF-kappa B pathways in monocytes/macrophages
- Authors
- Shim, Young-Jun; Kang, Byeong-Ho; Jeon, Hye-Sook; Park, In-Sun; Lee, Ki-Up; Lee, In-Kyu; Park, Gil-Hong; Lee, Kyung-Mi; Schedin, Pepper; Min, Bon-Hong
- Issue Date
- 10월-2011
- Publisher
- FEDERATION AMER SOC EXP BIOL
- Keywords
- MMP-9; glycosylation; ECM remodeling; tumor invasion; inflammation
- Citation
- JOURNAL OF LEUKOCYTE BIOLOGY, v.90, no.4, pp.761 - 769
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF LEUKOCYTE BIOLOGY
- Volume
- 90
- Number
- 4
- Start Page
- 761
- End Page
- 769
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/111419
- DOI
- 10.1189/jlb.0311110
- ISSN
- 0741-5400
- Abstract
- Most solid tumor tissues possess a significant population of macrophages, which are known to be closely linked with tumor progression and metastasis. Clusterin has been reported to be overexpressed in various tumors and to have a tumor-promoting role. As clusterin induction and macrophage infiltration occur concurrently at the tumor site, it raises a possibility that clusterin may regulate the function of macrophages via facilitating ECM remodeling. Here, we demonstrate for the first time the expression of MMP-9 by clusterin in human primary monocytes as well as human and murine macrophage cell lines, THP-1, and Raw264.7. MMP-9 expression was accompanied by increased enzymatic activity, as revealed by gelatin zymography. The MMP-9 activity promoted by clusterin was found to be dependent on the activation of ERK1/2 and PI3K/Akt but not p38 or JNK pathways. Inhibition of PI3K activity did not affect the activation of ERK1/2 and vice versa, indicating that the two pathways were independently operated to stimulate MMP-9 activity. Moreover, clusterin facilitated nuclear translocation of NF-kappa B p65 along with I kappa B-alpha degradation and phosphorylation, which was critical for MMP-9 expression. As NF-kappa B is a central regulator of inflammation, clusterin may provide a molecular link between inflammation and cancer via up-regulating NF-kappa B and MMP-9. Collectively, these data highlight a novel role of clusterin as a stimulator for MMP-9 expression in macrophages, which may contribute to the tissue reorganization by serving as a modulator for ECM degradation. J. Leukoc. Biol. 90: 761-769; 2011.
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Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
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