Downregulation of CD147 by chitooligosaccharide inhibits MMP‑2 expression and suppresses the metastatic potential of human gastric cancer

Luo,Zhiguo; Dong,Xiaoxia; Ke,Qing; Duan,Qiwen; Shen,Li

doi:10.3892/ol.2014.2115

Downregulation of CD147 by chitooligosaccharide inhibits MMP‑2 expression and suppresses the metastatic potential of human gastric cancer

Authors:
- Zhiguo Luo
- Xiaoxia Dong
- Qing Ke
- Qiwen Duan
- Li Shen
View Affiliations

Affiliations: Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China, Department of Pharmacology, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
Published online on: May 7, 2014 https://doi.org/10.3892/ol.2014.2115
Pages: 361-366

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Metastasis is considered to be the major cause of mortality in patients with cancer, and gastric cancer is a highly metastatic cancer. In the present study, the anti‑metastatic activity of chitooligosaccharide (COS) in human gastric cancer cells and its underlying mechanism were investigated. It was found that COS significantly inhibited SGC‑7901 cell proliferation and metastasis in a dose‑dependent manner, as observed by MTT, wound‑healing and Transwell assays. Quantitative real‑time polymerase chain reaction and western blot analysis indicated that COS could decrease the expression of cluster of differentiation 147 (CD147) and subsequently reduce matrix metalloproteinase‑2 (MMP‑2) expression. A clear dose‑dependent inhibition of MMP‑2 activity was also observed in SGC‑7901 cells following treatment with COS in gelatin zymography experiments. Furthermore, overexpression of CD147 (when transfected with pEGFP‑C1 plasmid) in SGC‑7901 cells partially protected against COS‑induced inhibition of MMP‑2. The results of the present study demonstrated the potential of COS in suppressing gastric cancer metastasis, and that the CD147/MMP‑2 pathway may be involved as the key mechanism of its anti‑metastatic effect.

View Figures

View References

1	Zheng L, Qi T, Yang D, et al: microRNA-9 suppresses the proliferation, invasion and metastasis of gastric cancer cells through targeting cyclin D1 and Ets1. PLoS One. 8:e557192013.
2	Mehlen P and Puisieux A: Metastasis: a question of life or death. Nat Rev Cancer. 6:449–458. 2006.
3	Nagase H, Visse R and Murphy G: Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res. 69:562–573. 2006.
4	Murray G, Duncan M, Arbuckle E, Melvin W and Fothergill J: Matrix metalloproteinases and their inhibitors in gastric cancer. Gut. 43:791–797. 1998.
5	Partyka R, Gonciarz M, Jalowiecki P, Kokocinska D and Byrczek T: VEGF and metalloproteinase 2 (MMP 2) expression in gastric cancer tissue. Med Sci Monit. 18:BR130–BR134. 2012.
6	Zhou J, Zhu P, Jiang JL, et al: Involvement of CD147 in overexpression of MMP-2 and MMP-9 and enhancement of invasive potential of PMA-differentiated THP-1. BMC Cell Biol. 6:252005.
7	Tang W, Chang SB and Hemler ME: Links between CD147 function, glycosylation, and caveolin-1. Mol Biol Cell. 15:4043–4050. 2004.
8	Jiang JL, Chan HC, Zhou Q, et al: HAb18G/CD147-mediated calcium mobilization and hepatoma metastasis require both C-terminal and N-terminal domains. Cell Mol Life Sci. 61:2083–2091. 2004.
9	Voigt H, Vetter-Kauczok CS, Schrama D, Hofmann UB, Becker JC and Houben R: CD147 impacts angiogenesis and metastasis formation. Cancer Invest. 27:329–333. 2009.
10	Zheng HC, Takahashi H, Murai Y, et al: Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis. Br J Cancer. 95:1371–1378. 2006.
11	Wang B, Xu YF, He BS, et al: RNAi-mediated silencing of CD147 inhibits tumor cell proliferation, invasion and increases chemosensitivity to cisplatin in SGC7901 cells in vitro. J Exp Clin Cancer Res. 29:612010.
12	Li J, He J and Yu C: Chitosan oligosaccharide inhibits LPS-induced apoptosis of vascular endothelial cells through the BKCa channel and the p38 signaling pathway. Int J Mol Med. 30:157–164. 2012.
13	Lee JK, Lim HS and Kim JH: Cytotoxic activity of aminoderivatized cationic chitosan derivatives. Bioorg Med Chem Lett. 12:2949–2951. 2002.
14	Chen D, Wang Y, Zhang K, Jiao X, Yan B and Liang J: Antisense oligonucleotide against clusterin regulates human hepatocellular carcinoma invasion through transcriptional regulation of matrix metalloproteinase-2 and e-cadherin. Int J Mol Sci. 13:10594–10607. 2012.
15	Nam KS and Shon YH: Suppression of metastasis of human breast cancer cells by chitosan oligosaccharides. J Microbiol Biotechnol. 19:629–633. 2009.
16	Shen KT, Chen MH, Chan HY, Jeng JH and Wang YJ: Inhibitory effects of chitooligosaccharides on tumor growth and metastasis. Food Chem Toxicol. 47:1864–1871. 2009.
17	Karagozlu MZ, Kim JA, Karadeniz F, Kong CS and Kim SK: Anti-proliferative effect of aminoderivatized chitooligosaccharides on AGS human gastric cancer cells. Process Biochem. 45:1523–1528. 2010.
18	Rundhaug JE: Matrix metalloproteinases, angiogenesis, and cancer: commentary re: A. C. Lockhart et al., Reduction of wound angiogenesis in patients treated with BMS-275291, a broad spectrum matrix metalloproteinase inhibitor Clin Cancer Res, 9: 00-00, 2003. Clin Cancer Res. 9:551–554. 2003.
19	Kim MM and Kim SK: Chitooligosaccharides inhibit activation and expression of matrix metalloproteinase-2 in human dermal fibroblasts. FEBS Lett. 580:2661–2666. 2006.
20	Van Ta Q, Kim MM and Kim SK: Inhibitory effect of chitooligosaccharides on matrix metalloproteinase-9 in human fibrosarcoma cells (HT1080). Mar Biotechnol (NY). 8:593–599. 2006.
21	Rajapakse N, Kim MM, Mendis E, Huang R and Kim SK: Carboxylated chitooligosaccharides (CCOS) inhibit MMP-9 expression in human fibrosarcoma cells via down-regulation of AP-1. Biochim Biophys Acta. 1760:1780–1788. 2006.
22	Omi Y, Shibata N, Okamoto T, Obara T and Kobayashi M: The role of CD147 in the invasiveness of follicular thyroid carcinoma cells. Thyroid. 22:383–394. 2012.
23	Huang W, Luo WJ, Zhu P, et al: Modulation of CD147-induced matrix metalloproteinase activity: role of CD147 N-glycosylation. Biochem J. 449:437–448. 2013.
24	Li R, Pan Y, He B, et al: Downregulation of CD147 expression by RNA interference inhibits HT29 cell proliferation, invasion and tumorigenicity in vitro and in vivo. Int J Oncol. 43:1885–1894. 2013.
25	Chen L, Pan Y, Gu L, et al: ERK1/2 signalling pathway is involved in CD147-mediated gastric cancer cell line SGC7901 proliferation and invasion. Exp Biol Med (Maywood). 238:903–912. 2013.