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Matrix Metalloproteinase-14 Is a Negative Prognostic Marker for Patients with Gastric Cancer

Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Matrix metalloproteinase-14 (MMP-14) has been considered to play an important role in invasion and metastasis of human solid tumor.

Aim

The present study aimed to investigate the association of MMP-14 with overall survival in human gastric cancer.

Methods

Gastric cancer and adjacent normal specimens were collected from 205 patients who had not received neoadjuvant chemotherapy. MMP-14 expression was investigated by immunohistochemistry assay and staining evaluation results were analyzed statistically in relation to overall survival of patients.

Results

MMP-14 expression proved to be increased in gastric cancer compared with that in normal tissues. It was also proved that MMP-14 expression was associated with tumor invasion, metastasis, and TNM stage while no correlations were detected between MMP-14 expression and age, sex, differentiation status, or Lauren’s classification. Moreover, patients with gastric cancer of MMP-14-positive expression tend to have worse overall survival compared with those with MMP-14 negative expression.

Conclusions

The present study confirmed the over-expression of MMP-14 in human gastric cancer and its association with tumor progression. It also provided the first evidence that MMP-14 expression in gastric cancer was an independent negative prognostic factor of patients.

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References

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.

    Article  PubMed  Google Scholar 

  2. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  3. Lin Y, Ueda J, Kikuchi S, et al. Comparative epidemiology of gastric cancer between Japan and China. World J Gastroenterol. 2011;17:4421–4428.

    Article  PubMed  Google Scholar 

  4. Yang L. Incidence and mortality of gastric cancer in China. World J Gastroenterol. 2006;12:17–20.

    PubMed  Google Scholar 

  5. Parsons SL, Watson SA, Brown PD, et al. Matrix metalloproteinases. Br J Surg. 1997;84:160–166.

    Article  PubMed  CAS  Google Scholar 

  6. Curran S, Murray GI. Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis. Eur J Cancer. 2000;36:1621–1630.

    Article  PubMed  CAS  Google Scholar 

  7. Nagase H, Woessner JF Jr. Matrix metalloproteinases. J Biol Chem. 1999;274:21491–21494.

    Article  PubMed  CAS  Google Scholar 

  8. Curran S, Murray GI. Matrix metalloproteinases in tumour invasion and metastasis. J Pathol. 1999;189:300–308.

    Article  PubMed  CAS  Google Scholar 

  9. Stetler-Stevenson WG, Type IV. Collagenases in tumor invasion and metastasis. Cancer Metastasis Rev. 1990;9:289–303.

    Article  PubMed  CAS  Google Scholar 

  10. Aalinkeel R, Nair BB, Reynolds JL, et al. Overexpression of MMP-9 contributes to invasiveness of prostate cancer cell line LNCaP. Immunol Invest. 2011;40:447–464.

    Article  PubMed  CAS  Google Scholar 

  11. Kumar B, Koul S, Petersen J, et al. p38 mitogen-activated protein kinase-driven MAPKAPK2 regulates invasion of bladder cancer by modulation of MMP-2 and MMP-9 activity. Cancer Res. 2010;70:832–841.

    Article  PubMed  CAS  Google Scholar 

  12. Joergensen MT, Brünner N, De Muckadell OB. Comparison of circulating MMP-9, TIMP-1 and CA19-9 in the detection of pancreatic cancer. Anticancer Res. 2010;30:587–592.

    PubMed  CAS  Google Scholar 

  13. Zarrabi K, Dufour A, Li J, et al. Inhibition of matrix metalloproteinase 14 (MMP-14)-mediated cancer cell migration. J Biol Chem. 2011;286:33167–33177.

    Article  PubMed  CAS  Google Scholar 

  14. Maquoi E, Assent D, Detilleux J, et al. MT1-MMP protects breast carcinoma cells against type I collagen-induced apoptosis. Oncogene. 2012;31:480–493.

    Article  PubMed  CAS  Google Scholar 

  15. Kaitu’u-Lino TJ, Palmer KR, Whitehead CL, et al. MMP-14 is expressed in preeclamptic placentas and mediates release of soluble endoglin. Am J Pathol. 2012;180:888–894.

    Article  PubMed  Google Scholar 

  16. Shields MA, Dangi-Garimella S, Redig AJ, et al. Biochemical role of the collagen-rich tumour microenvironment in pancreatic cancer progression. Biochem J. 2012;441:541–552.

    Article  PubMed  CAS  Google Scholar 

  17. Krantz SB, Shields MA, Dangi-Garimella S, et al. MT1–MMP cooperates with Kras(G12D) to promote pancreatic fibrosis through increased TGF-β signaling. Mol Cancer Res. 2011;9:1294–1304.

    Article  PubMed  CAS  Google Scholar 

  18. Woenne EC, Lederle W, Zwick S, et al. MMP inhibition blocks fibroblast-dependent skin cancer invasion, reduces vascularization and alters VEGF-A and PDGF-BB expression. Anticancer Res. 2010;30:703–711.

    PubMed  CAS  Google Scholar 

  19. Niewiarowska J, Brézillon S, Sacewicz-Hofman I, et al. Lumican inhibits angiogenesis by interfering with α2β1 receptor activity and downregulating MMP-14 expression. Thromb Res. 2011;128:452–457.

    Article  PubMed  CAS  Google Scholar 

  20. Crispi S, Calogero RA, Santini M, et al. Global gene expression profiling of human pleural mesotheliomas: identification of matrix metalloproteinase 14 (MMP-14) as potential tumour target. PLoS One. 2009;4:e7016.

    Article  PubMed  Google Scholar 

  21. Wang L, Yuan J, Tu Y, et al. Co-expression of MMP-14 and MMP-19 predicts poor survival in human glioma. Clin Transl Oncol. 2012. doi:10.1007/s12094-012-0900-5.

  22. Zhang H, Liu M, Sun Y, Lu J. MMP-14 can serve as a prognostic marker in patients with supraglottic cancer. Eur Arch Otorhinolaryngol. 2009;266:1427–1434.

    Article  PubMed  Google Scholar 

  23. Têtu B, Brisson J, Wang CS, et al. The influence of MMP-14, TIMP-2 and MMP-2 expression on breast cancer prognosis. Breast Cancer Res. 2006;8:R28.

    Article  PubMed  Google Scholar 

  24. Kubben FJ, Sier CF, van Duijn W, et al. Matrix metalloproteinase-2 is a consistent prognostic factor in gastric cancer. Br J Cancer. 2006;94:1035–1040.

    Article  PubMed  CAS  Google Scholar 

  25. Chu D, Zhang Z, Li Y, Zheng J, et al. Matrix metalloproteinase-9 is associated with disease-free survival and overall survival in patients with gastric cancer. Int J Cancer. 2011;129:887–895.

    Article  PubMed  CAS  Google Scholar 

  26. Rhodes A, Jasani B, Barnes DM, et al. Reliability of immunohistochemical demonstration of oestrogen receptors in routine practice: interlaboratory variance in the sensitivity of detection and evaluation of scoring systems. J Clin Pathol. 2000;53:125–130.

    Article  PubMed  CAS  Google Scholar 

  27. Curran S, Dundas SR, Buxton J, et al. Matrix metalloproteinase/tissue inhibitors of matrix metalloproteinase phenotype identifies poor prognosis colorectal cancers. Clin Cancer Res. 2004;10:8229–8234.

    Article  PubMed  CAS  Google Scholar 

  28. Lyall MS, Dundas SR, Curran S, Murray GI. Profiling markers of prognosis in colorectal cancer. Clin Cancer Res. 2006;12:1184–1191.

    Article  PubMed  CAS  Google Scholar 

  29. Peng ZR, Zhong WH, Liu J, Xiao PT. Effects of the combination of hyperbaric oxygen and 5-fluorouracil on proliferation and metastasis of human nasopharyngeal carcinoma CNE-2Z cells. Undersea Hyperb Med. 2010;37:141–150.

    PubMed  CAS  Google Scholar 

  30. Coskun U, Yamac D, Gulbahar O, et al. Locally advanced breast carcinoma treated with neoadjuvant chemotherapy: are the changes in serum levels of YKL-40, MMP-2 and MMP-9 correlated with tumor response? Neoplasma. 2007;54:348–352.

    PubMed  CAS  Google Scholar 

  31. Wang W, McLeod HL, Cassidy J. Disulfiram-mediated inhibition of NF-kappaB activity enhances cytotoxicity of 5-fluorouracil in human colorectal cancer cell lines. Int J Cancer. 2003;104:504–511.

    Article  PubMed  CAS  Google Scholar 

  32. Tamatani T, Azuma M, Ashida Y, et al. Enhanced radiosensitization and chemosensitization in NF-kappaB-suppressed human oral cancer cells via the inhibition of gamma-irradiation- and 5-FU-induced production of IL-6 and IL-8. Int J Cancer. 2004;108:912–921.

    Article  PubMed  CAS  Google Scholar 

  33. Kyllönen H, Pasanen AK, Kuittinen O, et al. Lack of prognostic value of MMP-9 expression and immunohistochemically defined germinal center phenotype in patients with diffuse large B-cell lymphoma treated with modern chemotherapy with or without CD20 antibody. Leuk Lymphoma. 2009;50:1301–1307.

    Article  PubMed  Google Scholar 

  34. Murray GI, Duncan ME, Arbuckle E, et al. Matrix metalloproteinases and their inhibitors in gastric cancer. Gut. 1998;43:791–797.

    Article  PubMed  CAS  Google Scholar 

  35. Puig-Costa M, Oliveras-Ferraros C, Flaquer S, et al. Antibody microarray-based technology to rapidly define matrix metalloproteinase (MMP) signatures in patients undergoing resection for primary gastric carcinoma. J Surg Oncol. 2011;104:106–109.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 31270812).

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Correspondence to Gang Ji.

Additional information

Liang He, Dake Chu, Xia Li, Jianyong Zheng, and Shanhong Liu contributed equally to this work.

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He, L., Chu, D., Li, X. et al. Matrix Metalloproteinase-14 Is a Negative Prognostic Marker for Patients with Gastric Cancer. Dig Dis Sci 58, 1264–1270 (2013). https://doi.org/10.1007/s10620-012-2513-9

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  • DOI: https://doi.org/10.1007/s10620-012-2513-9

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