+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Catalytic activity of Matrix metalloproteinase-19 is essential for tumor suppressor and anti-angiogenic activities in nasopharyngeal carcinoma

Catalytic activity of Matrix metalloproteinase-19 is essential for tumor suppressor and anti-angiogenic activities in nasopharyngeal carcinoma

International Journal of Cancer 129(8): 1826-1837

The association of Matrix metalloproteinase-19 (MMP19) in the development of nasopharyngeal carcinoma (NPC) was identified from differential gene profiling, which showed MMP19 was one of the candidate genes down-regulated in the NPC cell lines. In this study, quantitative RT-PCR and Western blot analysis showed MMP19 was down-regulated in all seven NPC cell lines. By tissue microarray immunohistochemical staining, MMP19 appears down-regulated in 69.7% of primary NPC specimens. Allelic deletion and promoter hypermethylation contribute to MMP19 down-regulation. We also clearly demonstrate that the catalytic activity of MMP19 plays an important role in antitumor and antiangiogenesis activities in comparative studies of the wild-type and the catalytically inactive mutant MMP19. In the in vivo tumorigenicity assay, only the wild-type (WT), but not mutant, MMP19 transfectants suppress tumor formation in nude mice. In the in vitro colony formation assay, WT MMP19 dramatically reduces colony-forming ability of NPC cell lines, when compared to the inactive mutant. In the tube formation assay of human umbilical vein endothelial cells and human microvascular endothelial cells (HMEC-1), secreted WT MMP19, but not mutant MMP19, induces reduction of tube-forming ability in endothelial cells with decreased vascular endothelial growth factor (VEGF) in conditioned media detected by enzyme-linked immunosorbent assay (ELISA). The anti-angiogenic activity of WT MMP19 is correlated with suppression of tumor formation. These results now clearly show that catalytic activity of MMP19 is essential for its tumor suppressive and anti-angiogenic functions in NPC.

(PDF emailed within 0-6 h: $19.90)

Accession: 051968702

Download citation: RISBibTeXText

PMID: 21165953

DOI: 10.1002/ijc.25855

Related references

Anti-metastatic and anti-angiogenic activities of a new matrix metalloproteinase inhibitor, TN-6b. European Journal of Cancer 39(11): 1632-1641, July, 2003

The anti-angiogenic effect of halofuginone Inhibition of collagen type I tube formation, matrix metalloproteinase-2 activities and extracellular matrix deposition. Blood 96(11 Part 1): 34a, November 16, 2000

Anti-tumor angiogenic effect of a matrix metalloproteinase inhibitor MMI270. Anticancer Research 23(1a): 411-417, 2003

Anti-angiogenic and anti-tumor invasive activities of tissue inhibitor of metalloproteinase-3 from shark, Scyliorhinus torazame. Biochimica et Biophysica Acta 1620(1-3): 59-64, 17 March, 2003

Anti-invasive activity of sanguinarine through modulation of tight junctions and matrix metalloproteinase activities in MDA-MB-231 human breast carcinoma cells. Chemico-Biological Interactions 179(2-3): 185-191, 2008

Correlation between expression of extracellular matrix metalloproteinase inducer and matrix metalloproteinase-2 and cervical lymph node metastasis of nasopharyngeal carcinoma. Annals of Otology, Rhinology, and Laryngology 122(3): 210-215, 2013

Expression of tumor metastasis-suppressor gene KiSS-1 and matrix metalloproteinase-9 in portal vein tumor thrombus of hepatocellular carcinoma. Ai Zheng 26(6): 591-595, 2007

Exercise modulates platelet-nasopharyngeal carcinoma cell aggregation and subsequent tissue factor and matrix metalloproteinase activities. Journal of Applied Physiology 103(3): 763-770, 2007

An immunoconjugate targeting matrix metalloproteinase shows highly potent cytotoxicity and anti-angiogenic activity. Proceedings of the American Association for Cancer Research Annual Meeting 42: 290, March, 2001

Strategy for the clinical application of anti-angiogenic therapy against hepatocarcinogenesis and proliferation of hepatocellular carcinoma Mainly focused on matrix metalloproteinase inhibitor and HCV. Hepatology 32(4 Pt 2): 478A, October, 2000

Peptide inhibition of catalytic and noncatalytic activities of matrix metalloproteinase-9 blocks tumor cell migration and invasion. Journal of Biological Chemistry 279(28): 29589-29597, 2004

Anti-invasive activity of ethanol extracts of Ganoderma lucidum through tightening of tight junctions and inhibition of matrix metalloproteinase activities in human gastric carcinoma cells. Journal of Acupuncture and Meridian Studies 4(4): 225-235, 2012

Anti-invasive Activity of Ethanol Extracts ofGanoderma lucidumthrough Tightening of Tight Junctions and Inhibition of Matrix Metalloproteinase Activities in Human Gastric Carcinoma Cells. 2011