Saudi Journal of Gastroenterology
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Year : 2011  |  Volume : 17  |  Issue : 5  |  Page : 299-300
MMP7 Polymorphisms - A new tool in molecular pathology to understand esophageal cancer


Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

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Date of Web Publication6-Sep-2011
 

How to cite this article:
Bavi PP, Bu R, Uddin S, Al-Kuraya KS. MMP7 Polymorphisms - A new tool in molecular pathology to understand esophageal cancer. Saudi J Gastroenterol 2011;17:299-300

How to cite this URL:
Bavi PP, Bu R, Uddin S, Al-Kuraya KS. MMP7 Polymorphisms - A new tool in molecular pathology to understand esophageal cancer. Saudi J Gastroenterol [serial online] 2011 [cited 2019 Sep 17];17:299-300. Available from: http://www.saudijgastro.com/text.asp?2011/17/5/299/84479


Esophageal cancer is one of the most aggressive malignant gastrointestinal tumors and the majority of esophageal cancers are squamous cell carcinoma (ESCC) or adenocarcinoma (AC). In the Asian population almost all cases of esophageal cancer are squamous cell cancers, whereas in the Western world adenocarcinoma occurs more often and its incidence has risen over recent decades (source: GLOBOCAN; http://globocan.iarc.fr ). Patients with ESCC have a propensity to present with extensive local invasion and regional lymph node metastasis thereby leading to a worse prognosis than those with other digestive tract cancers even after curative surgical resection. [1] In the multi-step process of carcinogenesis, tumor invasion step requires the degradation or breakdown of the extracellular matrix (ECM) and connective tissue surrounding the tumor. [2] In this issue of the Saudi Journal of Gastroenterology, Malik and co-workers [3] assessed the association of MMP-7 (-181A>G) polymorphism with the esophageal cancer in the Kashmir Valley of India.

MMPs are a family of zinc-dependent proteolytic enzymes capable of degrading the ECM, and have been demonstrated to be involved in carcinoma invasion and metastasis by degrading the extracellular components. [4],[5],[6] MMP-7 is the smallest molecule of the MMPs. It can degrade laminin, type IV collagen, and entactin, which are the main components of the basement membrane, and activate other important MMPs (MMP-1, MMP-2, and MMP-9). [7],[8] It can also inactivate α1-antitrypsin, which augments the serine protease activity, and thus activates MMPs indirectly. [9] MMP7 is overexpressed in a variety of epithelial and mesenchymal tumors, such as esophagus, colon, liver, renal, and pancreas. Its expression is correlated with tumor progression, metastasis, and unfavorable prognosis in the human esophageal carcinoma, colon, and gastric carcinoma. [10],[11],[12] On the other hand, MMP-7 was also found to contribute to early tumor development especially in tumors of gastrointestinal tract. [4],[13] There are at least three regulatory mechanisms that may influence activities of MMPs - regulation of transcription, activation of latent MMPs, and inhibition of MMP function by tissue inhibitors of metalloproteinases. However, the most important step may be transcriptional regulation, since most MMP genes express only when active physiological or pathological tissue remodeling takes place.

Growing evidence indicates that natural sequence variations in promoters of the MMP genes may result in variable expression of MMPs in different individuals. These polymorphisms have been associated with susceptibility to some diseases including cancers. [14],[15] In the promoter region of the MMP-7 gene, two single nucleotide polymorphisms (SNPs), an A to G transition at the -181 base pair position (-181A/G) and a C to T transition at the -153 base pair position (-153C/T), have been proved to be functional in vitro and may influence coronary artery dimensions. [16] Recently, the -181A/G SNP has been associated with increased risk of development and metastasis of colorectal cancer while the -153C/T polymorphism seems to be less involved in susceptibility to this tumor. [17] However, another study suggested MMP-7 -181A/G polymorphism might be a candidate marker for predicting individuals with a higher risk to develop ESCC, gastric carcinoma, and non small cell lung carcinoma. [18] Most recently, the author and his co-workers reported that the individual living in the Kashmir Valley carrying -181 GG genotype was associated with high risk of gastric cancer, indicating that common MMP-7 (-181A>G) genetic polymorphism may contribute to squamous cell gastric cancer susceptibility in the Kashmir valley. [19]

Malik and co-workers assessed the association of MMP-7 (-181A>G) polymorphism with the esophageal cancer in the Kashmir Valley of India. The investigators found that the individual carrying GG genotype had 2.17 fold increased risk to develop EC while the individual with A allele had 2.16 fold lower risk of EC. Moreover, the author and his colleagues found that GG genotype was associated with higher risk to develop ESCC, not adenocarcinoma of esophagus cancer while environmental factors (salted tea and smoking) did not modulate cancer risk by MMP-7 (−181A>G) genotype. All together, these data are very interesting and warrant further large-scale, case-controlled studies of MMP-7 (-181A>G) polymorphism as a biomarker to predict high-risk individuals for the development of EC. Treatment of esophageal carcinoma will evolve with the strides made in molecular diagnostics and targeted therapy. Commonly occurring SNPs should be meticulously studied in populations where there is paucity of such data, to learn more about the molecular signature of the tumors.

 
   References Top

1.Wang LS, Chow KC, Wu YC, Li WY, Huang MH. Detection of Epstein-Barr virus in esophageal squamous cell carcinoma in Taiwan. Am J Gastroenterol 1999;94:2834-9.  Back to cited text no. 1
    
2.Sternlicht MD, Werb Z. How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 2001;17:463-516.  Back to cited text no. 2
    
3.Malik MA, Sharma KL, Zargar SA, Mittal B. Association of Matrix Metalloproteinase-7 (-181A>G) Polymorphism with Risk of Esophageal Squamous Cell Carcinoma in Kashmir Valley. Saudi J Gastroenterol 2011;17:301-6.  Back to cited text no. 3
  Medknow Journal  
4.Wilson CL, Heppner KJ, Labosky PA, Hogan BL, Matrisian LM. Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin. Proc Natl Acad Sci U S A 1997;94:1402-7.  Back to cited text no. 4
    
5.Ohashi K, Nemoto T, Nakamura K, Nemori R. Increased expression of matrix metalloproteinase 7 and 9 and membrane type 1-matrix metalloproteinase in esophageal squamous cell carcinomas. Cancer 2000;88:2201-9.  Back to cited text no. 5
    
6.Adachi Y, Itoh F, Yamamoto H, Matsuno K, Arimura Y, Kusano M, et al. Matrix metalloproteinase matrilysin (MMP-7) participates in the progression of human gastric and esophageal cancers. Int J Oncol 1998;13:1031-5.  Back to cited text no. 6
    
7.Crabbe T, Smith B, O'Connell J, Docherty A. Human progelatinase A can be activated by matrilysin. FEBS Lett 1994;345:14-6.  Back to cited text no. 7
    
8.Sang QA, Bodden MK, Windsor LJ. Activation of human progelatinase A by collagenase and matrilysin: Activation of procollagenase by matrilysin. J Protein Chem 1996;15:243-53.  Back to cited text no. 8
    
9.Sires UI, Murphy G, Baragi VM, Fliszar CJ, Welgus HG, Senior RM. Matrilysin is much more efficient than other matrix metalloproteinases in the proteolytic inactivation of alpha 1-antitrypsin. Biochem Biophys Res Commun 1994;204:613-20.  Back to cited text no. 9
    
10.Honda M, Mori M, Ueo H, Sugimachi K, Akiyoshi T. Matrix metalloproteinase-7 expression in gastric carcinoma. Gut 1996;39:444-8.  Back to cited text no. 10
    
11.Szarvas T, Becker M, vom Dorp F, Gethmann C, Totsch M, Bankfalvi A, et al. Matrix metalloproteinase-7 as a marker of metastasis and predictor of poor survival in bladder cancer. Cancer Sci 2010;101:1300-8.  Back to cited text no. 11
    
12.Mori M, Barnard GF, Mimori K, Ueo H, Akiyoshi T, Sugimachi K. Overexpression of matrix metalloproteinase-7 mRNA in human colon carcinomas. Cancer 1995;75 (6 Suppl):1516-9.  Back to cited text no. 12
    
13.Witty JP, McDonnell S, Newell KJ, Cannon P, Navre M, Tressler RJ, et al. Modulation of matrilysin levels in colon carcinoma cell lines affects tumorigenicity in vivo. Cancer Res 1994;54:4805-12.  Back to cited text no. 13
    
14.Zhang J, Jin X, Fang S, Li Y, Wang R, Guo W, et al. The functional SNP in the matrix metalloproteinase-3 promoter modifies susceptibility and lymphatic metastasis in esophageal squamous cell carcinoma but not in gastric cardiac adenocarcinoma. Carcinogenesis 2004;25:2519-24.  Back to cited text no. 14
    
15.Yu C, Pan K, Xing D, Liang G, Tan W, Zhang L, et al. Correlation between a single nucleotide polymorphism in the matrix metalloproteinase-2 promoter and risk of lung cancer. Cancer Res 2002;62:6430-3.  Back to cited text no. 15
    
16.Jormsjo S, Whatling C, Walter DH, Zeiher AM, Hamsten A, Eriksson P. Allele-specific regulation of matrix metalloproteinase-7 promoter activity is associated with coronary artery luminal dimensions among hypercholesterolemic patients. Arterioscler Thromb Vasc Biol 2001;21:1834-9.  Back to cited text no. 16
    
17.Ghilardi G, Biondi ML, Erario M, Guagnellini E, Scorza R. Colorectal carcinoma susceptibility and metastases are associated with matrix metalloproteinase-7 promoter polymorphisms. Clin Chem 2003;49:1940-2.  Back to cited text no. 17
    
18.Zhang J, Jin X, Fang S, Wang R, Li Y, Wang N, et al. The functional polymorphism in the matrix metalloproteinase-7 promoter increases susceptibility to esophageal squamous cell carcinoma, gastric cardiac adenocarcinoma and non-small cell lung carcinoma. Carcinogenesis 2005;26:1748-53.  Back to cited text no. 18
    
19.Malik MA, Zargar SA, Mittal B. Role of the Metalloproteinase-7 (181A>G) Polymorphism in Gastric Cancer Susceptibility: A Case Control Study in Kashmir Valley. Asian Pac J Cancer Prev 2011;12:73-6.  Back to cited text no. 19
    

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Correspondence Address:
Khawla S Al-Kuraya
Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Centre, Riyadh
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-3767.84479

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