MMP-2 and MMP-9 in Normal Mucosa Are Independently Associated with Outcome of Colorectal Cancer Patients

Overview

Journal Br J Cancer

Specialty Oncology

Date 2012 Apr 5

PMID 22472880

Citations 35

Authors

A M J Langers

H W Verspaget

L J A C Hawinkels

F J G M Kubben

W van Duijn

J J van der Reijden

J C H Hardwick

D W Hommes

C F M Sier

Affiliations

Soon will be listed here.

Abstract

Background: Upregulation of the matrix metalloproteinases MMP-2 and MMP-9 in various cancers has been associated with worse survival of the patients.

Methods: We assessed MMP-2 and MMP-9 levels in normal colorectal mucosa from colorectal cancer patients in relation to the course of the disease.

Results: A high protein expression of MMP-2 as well as MMP-9 in normal mucosa was found to be correlated with worse 5-year survival. The combination of both parameters was an even stronger prognostic factor. These protein levels were found not to be related to the corresponding single nucleotide polymorphisms of MMP-2 (-1306C>T) and MMP-9 (-1562C>T). Multivariate analyses indicated that the MMP-2 and MMP-9 levels in normal mucosa are prognostic for survival, independent of TNM classification.

Conclusion: MMP-2 and MMP-9 levels in normal mucosa are indicative of the course of disease in colorectal cancer patients.

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References

Ganesh S, Sier C, Griffioen G, Vloedgraven H, de Boer A, Welvaart K . Prognostic relevance of plasminogen activators and their inhibitors in colorectal cancer. Cancer Res. 1994; 54(15):4065-71. View

Kubben F, Sier C, Meijer M, van den Berg M, van der Reijden J, Griffioen G . Clinical impact of MMP and TIMP gene polymorphisms in gastric cancer. Br J Cancer. 2006; 95(6):744-51. PMC: 2360506. DOI: 10.1038/sj.bjc.6603307. View

Bellone G, Solerio D, Chiusa L, Brondino G, Carbone A, Prati A . Transforming growth factor-beta binding receptor endoglin (CD105) expression in esophageal cancer and in adjacent nontumorous esophagus as prognostic predictor of recurrence. Ann Surg Oncol. 2007; 14(11):3232-42. DOI: 10.1245/s10434-007-9528-z. View

Fox S, WHALEN G, Sanders M, Burleson J, Jennings K, Kurtzman S . Angiogenesis in normal tissue adjacent to colon cancer. J Surg Oncol. 1999; 69(4):230-4. DOI: 10.1002/(sici)1096-9098(199812)69:4<230::aid-jso7>3.0.co;2-q. View

Zhang B, Ye S, Herrmann S, Eriksson P, de Maat M, Evans A . Functional polymorphism in the regulatory region of gelatinase B gene in relation to severity of coronary atherosclerosis. Circulation. 1999; 99(14):1788-94. DOI: 10.1161/01.cir.99.14.1788. View

Meijer M, Mieremet-Ooms M, van Duijn W, van der Zon A, Hanemaaijer R, Verheijen J . Effect of the anti-tumor necrosis factor-alpha antibody infliximab on the ex vivo mucosal matrix metalloproteinase-proteolytic phenotype in inflammatory bowel disease. Inflamm Bowel Dis. 2007; 13(2):200-10. DOI: 10.1002/ibd.20051. View

Hawinkels L, Zuidwijk K, Verspaget H, de Jonge-Muller E, van Duijn W, Ferreira V . VEGF release by MMP-9 mediated heparan sulphate cleavage induces colorectal cancer angiogenesis. Eur J Cancer. 2008; 44(13):1904-13. DOI: 10.1016/j.ejca.2008.06.031. View

Price S, Greaves D, Watkins H . Identification of novel, functional genetic variants in the human matrix metalloproteinase-2 gene: role of Sp1 in allele-specific transcriptional regulation. J Biol Chem. 2000; 276(10):7549-58. DOI: 10.1074/jbc.M010242200. View

Mulder T, Verspaget H, Janssens A, de Bruin P, Griffioen G, Lamers C . Neoplasia-related changes of two copper (Cu)/zinc (Zn) proteins in the human colon. Free Radic Biol Med. 1990; 9(6):501-6. DOI: 10.1016/0891-5849(90)90128-6. View

10.

Hawinkels L, Kuiper P, Wiercinska E, Verspaget H, Liu Z, Pardali E . Matrix metalloproteinase-14 (MT1-MMP)-mediated endoglin shedding inhibits tumor angiogenesis. Cancer Res. 2010; 70(10):4141-50. DOI: 10.1158/0008-5472.CAN-09-4466. View

11.

Edelstein P, Thompson S, Davies R . Altered intracellular calcium regulation in human colorectal cancers and in "normal" adjacent mucosa. Cancer Res. 1991; 51(16):4492-4. View

12.

Hothorn L . Biostatistical analysis of the micronucleus mutagenicity assay based on the assumption of a mixing distribution. Environ Health Perspect. 1994; 102 Suppl 1:121-5. PMC: 1566887. DOI: 10.1289/ehp.94102s1121. View

13.

Boland C, Kim Y . Transitional mucosa of the colon and tumor growth factors. Med Hypotheses. 1987; 22(3):237-43. DOI: 10.1016/0306-9877(87)90189-7. View

14.

Langers A, Verspaget H, Hommes D, Sier C . Single-nucleotide polymorphisms of matrix metalloproteinases and their inhibitors in gastrointestinal cancer. World J Gastrointest Oncol. 2011; 3(6):79-98. PMC: 3124635. DOI: 10.4251/wjgo.v3.i6.79. View

15.

Ganesh S, Sier C, Heerding M, van Krieken J, Griffioen G, Welvaart K . Contribution of plasminogen activators and their inhibitors to the survival prognosis of patients with Dukes' stage B and C colorectal cancer. Br J Cancer. 1997; 75(12):1793-801. PMC: 2223607. DOI: 10.1038/bjc.1997.306. View

16.

Miller S, Dykes D, Polesky H . A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988; 16(3):1215. PMC: 334765. DOI: 10.1093/nar/16.3.1215. View

17.

Gao Q, Meijer M, Kubben F, Sier C, Kruidenier L, van Duijn W . Expression of matrix metalloproteinases-2 and -9 in intestinal tissue of patients with inflammatory bowel diseases. Dig Liver Dis. 2005; 37(8):584-92. DOI: 10.1016/j.dld.2005.02.011. View

18.

Pretlow T, Barrow B, Ashton W, ORiordan M, Pretlow T, Jurcisek J . Aberrant crypts: putative preneoplastic foci in human colonic mucosa. Cancer Res. 1991; 51(5):1564-7. View

19.

Zucker S, Vacirca J . Role of matrix metalloproteinases (MMPs) in colorectal cancer. Cancer Metastasis Rev. 2004; 23(1-2):101-17. DOI: 10.1023/a:1025867130437. View

20.

Langers A, Sier C, Hawinkels L, Kubben F, van Duijn W, van der Reijden J . MMP-2 geno-phenotype is prognostic for colorectal cancer survival, whereas MMP-9 is not. Br J Cancer. 2008; 98(11):1820-3. PMC: 2410128. DOI: 10.1038/sj.bjc.6604380. View