Skip to main content

MMP-14 overexpression correlates with poor prognosis in non-small cell lung cancer

Tumor Biology volume 35, pages 9815–9821 (2014)Cite this article

Abstract

Matrix metalloproteinase-14 (MMP-14) has been demonstrated to play an important role in tumor progression. The aim of this study was to analyze the correlation between MMP-14 expression and clinicopathologic features and its prognostic significance in non-small cell lung cancer (NSCLC). Immunohistochemical staining for MMP-14 protein was performed in 104 patients with NSCLC. High levels of MMP-14 protein were positively correlated with the status of clinical stage (I–II vs. III–IV; P < 0.001), N classification (N0–N1 vs. N2–N3; P < 0.001), distant metastasis (no vs. yes; P = 0.014), and differentiated degree (high vs. low or undifferentiated; P = 0.001). The patients with higher MMP-14 expression of protein had shorter survival time than patients with low MMP-14 expression. Multivariate analysis indicated that the level of MMP-14 expression was an independent prognostic indicator (P < 0.001) for the survival of patients with NSCLC. In conclusion, MMP-14 is a potential unfavorable prognostic factor for patients with NSCLC.

This is a preview of subscription content, access via your institution.

Fig. 1

Abbreviations

MMP-14:

Matrix metalloproteinase-14

NSCLC:

Non-small cell lung cancer

OS:

Overall survival

IHC:

Immunohistochemistry

References

  1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29. doi:10.3322/caac.21208.

    Article  PubMed  Google Scholar 

  2. She J, Yang P, Hong Q, Bai C. Lung cancer in China: challenges and interventions. Chest. 2013;143(4):1117–26. doi:10.1378/chest.11-2948.

    Article  PubMed  Google Scholar 

  3. Yang P, Allen MS, Aubry MC, Wampfler JA, Marks RS, Edell ES, et al. Clinical features of 5,628 primary lung cancer patients: experience at Mayo Clinic from 1997 to 2003. Chest. 2005;128(1):452–62. doi:10.1378/chest.128.1.452.

    Article  PubMed  Google Scholar 

  4. Deng YP, Li W, Li YL, Xu H, Liang SS, Zhang LH, et al. MT1-MMP up-regulates VEGF expression in human breast carcinoma MCF-7 cells and induces tumor angiogenesis [article in Chinese]. Chin J Oncol. 2009;31(10):727–31.

    CAS  Google Scholar 

  5. Jiang WG, Davies G, Martin TA, Parr C, Watkins G, Mason MD, et al. Expression of membrane type-1 matrix metalloproteinase, MT1-MMP in human breast cancer and its impact on invasiveness of breast cancer cells. Int J Mol Med. 2006;17(4):583–90.

    PubMed  Google Scholar 

  6. Takino T, Tsuge H, Ozawa T, Sato H. MT1-MMP promotes cell growth and ERK activation through c-Src and paxillin in three-dimensional collagen matrix. Biochem Biophys Res Commun. 2010;396(4):1042–7. doi:10.1016/j.bbrc.2010.05.059.

    Article  CAS  PubMed  Google Scholar 

  7. Tolde O, Rosel D, Mierke CT, Pankova D, Folk P, Vesely P, et al. Neoplastic progression of the human breast cancer cell line G3S1 is associated with elevation of cytoskeletal dynamics and upregulation of MT1-MMP. Int J Oncol. 2010;36(4):833–9.

    CAS  PubMed  Google Scholar 

  8. Suojanen J, Salo T, Koivunen E, Sorsa T, Pirila E. A novel and selective membrane type-1 matrix metalloproteinase (MT1-MMP) inhibitor reduces cancer cell motility and tumor growth. Cancer Biol Ther. 2009;8(24):2362–70.

    Article  CAS  PubMed  Google Scholar 

  9. Xu M, Wang YZ. miR133a suppresses cell proliferation, migration and invasion in human lung cancer by targeting MMP14. Oncol Rep. 2013;30(3):1398–404. doi:10.3892/or.2013.2548.

    CAS  PubMed  Google Scholar 

  10. Atkinson JM, Pennington CJ, Martin SW, Anikin VA, Mearns AJ, Loadman PM, et al. Membrane type matrix metalloproteinases (MMPs) show differential expression in non-small cell lung cancer (NSCLC) compared to normal lung: correlation of MMP-14 mRNA expression and proteolytic activity. Eur J Cancer. 2007;43(11):1764–71. doi:10.1016/j.ejca.2007.05.009.

    Article  CAS  PubMed  Google Scholar 

  11. Demidyuk IV, Shubin AV, Gasanov EV, Kurinov AM, Demkin VV, Vinogradova TV, et al. Alterations in gene expression of proprotein convertases in human lung cancer have a limited number of scenarios. PLoS One. 2013;8(2):e55752. doi:10.1371/journal.pone.0055752.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  12. Peng CW, Wang LW, Fang M, Yang GF, Li Y, Pang DW. Combined features based on MT1-MMP expression, CD11b + immunocytes density and LNR predict clinical outcomes of gastric cancer. J Transl Med. 2013;11:153. doi:10.1186/1479-5876-11-153.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  13. Akanuma N, Hoshino I, Akutsu Y, Murakami K, Isozaki Y, Maruyama T, et al. MicroRNA-133a regulates the mRNAs of two invadopodia-related proteins, FSCN1 and MMP14, in esophageal cancer. Br J Cancer. 2014;110(1):189–98. doi:10.1038/bjc.2013.676.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  14. Tetu B, Brisson J, Wang CS, Lapointe H, Beaudry G, Blanchette C, et al. The influence of MMP-14, TIMP-2 and MMP-2 expression on breast cancer prognosis. Breast Cancer Res : BCR. 2006;8(3):R28. doi:10.1186/bcr1503.

    PubMed Central  Article  PubMed  Google Scholar 

  15. Crispi S, Calogero RA, Santini M, Mellone P, Vincenzi B, Citro G, 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(9):e7016. doi:10.1371/journal.pone.0007016.

    PubMed Central  Article  PubMed  Google Scholar 

  16. Wang L, Yuan J, Tu Y, Mao X, He S, Fu G, et al. Co-expression of MMP-14 and MMP-19 predicts poor survival in human glioma. Clin Transl Oncol. 2013;15(2):139–45. doi:10.1007/s12094-012-0900-5.

    Article  CAS  PubMed  Google Scholar 

  17. Trudel D, Fradet Y, Meyer F, Harel F, Tetu B. Membrane-type-1 matrix metalloproteinase, matrix metalloproteinase 2, and tissue inhibitor of matrix proteinase 2 in prostate cancer: identification of patients with poor prognosis by immunohistochemistry. Hum Pathol. 2008;39(5):731–9. doi:10.1016/j.humpath.2007.09.021.

    Article  CAS  PubMed  Google Scholar 

  18. 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(9):1427–34. doi:10.1007/s00405-009-0943-6.

    Article  PubMed  Google Scholar 

  19. Kondratiev S, Gnepp DR, Yakirevich E, Sabo E, Annino DJ, Rebeiz E, et al. Expression and prognostic role of MMP2, MMP9, MMP13, and MMP14 matrix metalloproteinases in sinonasal and oral malignant melanomas. Hum Pathol. 2008;39(3):337–43. doi:10.1016/j.humpath.2007.07.003.

    Article  CAS  PubMed  Google Scholar 

  20. Luo WR, Wu AB, Fang WY, Li SY, Yao KT. Nuclear expression of N-cadherin correlates with poor prognosis of nasopharyngeal carcinoma. Histopathology. 2012;61(2):237–46. doi:10.1111/j.1365-2559.2012.04212.x.

    Article  PubMed  Google Scholar 

  21. Li J, Guan HY, Gong LY, Song LB, Zhang N, Wu J, et al. Clinical significance of sphingosine kinase-1 expression in human astrocytomas progression and overall patient survival. Clin Cancer Res. 2008;14(21):6996–7003. doi:10.1158/1078-0432.ccr-08-0754.

    Article  CAS  PubMed  Google Scholar 

  22. Delassus GS, Cho H, Hoang S, Eliceiri GL. Many new down- and up-regulatory signaling pathways, from known cancer progression suppressors to matrix metalloproteinases, differ widely in cells of various cancers. J Cell Physiol. 2010;224(2):549–58. doi:10.1002/jcp.22157.

    Article  CAS  PubMed  Google Scholar 

  23. Chen TY, Li YC, Liu YF, Tsai CM, Hsieh YH, Lin CW, et al. Role of MMP14 gene polymorphisms in susceptibility and pathological development to hepatocellular carcinoma. Ann Surg Oncol. 2011;18(8):2348–56. doi:10.1245/s10434-011-1574-x.

    Article  PubMed  Google Scholar 

  24. Kettunen E, Anttila S, Seppanen JK, Karjalainen A, Edgren H, Lindstrom I, et al. Differentially expressed genes in nonsmall cell lung cancer: expression profiling of cancer-related genes in squamous cell lung cancer. Cancer Genet Cytogenet. 2004;149(2):98–106. doi:10.1016/s0165-4608(03)00300-5.

    Article  CAS  PubMed  Google Scholar 

  25. Udayakumar TS, Chen ML, Bair EL, Von Bredow DC, Cress AE, Nagle RB, et al. Membrane type-1-matrix metalloproteinase expressed by prostate carcinoma cells cleaves human laminin-5 beta3 chain and induces cell migration. Cancer Res. 2003;63(9):2292–9.

    CAS  PubMed  Google Scholar 

  26. Okada A, Bellocq JP, Rouyer N, Chenard MP, Rio MC, Chambon P, et al. Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas. Proc Natl Acad Sci U S A. 1995;92(7):2730–4.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  27. Munaut C, Noel A, Hougrand O, Foidart JM, Boniver J, Deprez M. Vascular endothelial growth factor expression correlates with matrix metalloproteinases MT1-MMP, MMP-2 and MMP-9 in human glioblastomas. Int J Cancer J Int du Cancer. 2003;106(6):848–55. doi:10.1002/ijc.11313.

    Article  CAS  Google Scholar 

  28. Yamamura T, Nakanishi K, Hiroi S, Kumaki F, Sato H, Aida S, et al. Expression of membrane-type-1-matrix metalloproteinase and metalloproteinase-2 in nonsmall cell lung carcinomas. Lung Cancer. 2002;35(3):249–55.

    Article  PubMed  Google Scholar 

  29. Wiegand S, Dunne AA, Muller HH, Mandic R, Barth P, Davis RK, et al. Metaanalysis of the significance of matrix metalloproteinases for lymph node disease in patients with head and neck squamous cell carcinoma. Cancer. 2005;104(1):94–100. doi:10.1002/cncr.21131.

    Article  CAS  PubMed  Google Scholar 

  30. Uzui H, Harpf A, Liu M, Doherty TM, Shukla A, Chai NN, et al. Increased expression of membrane type 3-matrix metalloproteinase in human atherosclerotic plaque: role of activated macrophages and inflammatory cytokines. Circulation. 2002;106(24):3024–30.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the funding from the National Natural Science Foundation of China (81201672).

Conflicts of interest

None

Author information

Affiliations

  1. Cancer Center, Affiliated Hospital of Guangdong Medical College, No. 57 People’s Avenue South, Zhanjiang, 524002, Guangdong, People’s Republic of China

    Yu-zhou Wang, Kun-peng Wu, Ai-bing Wu, Zhi-cheng Yang, Jin-mei Li, Yan-li Mo & Zhi-xiong Yang

  2. Department of Oncology, The First Affiliated Hospital, Jinan University, No. 613 Huangpu Road West, Guangzhou, 510630, Guangdong, People’s Republic of China

    Meng Xu

  3. Department of Respiratory Medicine, Affiliated Hospital of Guangdong Medical College, No. 57 People’s Avenue South, Zhanjiang, 524002, Guangdong, People’s Republic of China

    Bin Wu

  4. Cancer Center, Heyuan People’s Hospital, No. 733 Wenxiang Road, Heyuan, 517000, Guangdong, People’s Republic of China

    Kun-peng Wu

Authors
  1. Yu-zhou Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kun-peng Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ai-bing Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhi-cheng Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jin-mei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yan-li Mo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Meng Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bin Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Zhi-xiong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Meng Xu, Bin Wu or Zhi-xiong Yang.

Additional information

Yu-zhou Wang and Kun-peng Wu are co-first authors.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wang, Yz., Wu, Kp., Wu, Ab. et al. MMP-14 overexpression correlates with poor prognosis in non-small cell lung cancer. Tumor Biol. 35, 9815–9821 (2014). https://doi.org/10.1007/s13277-014-2237-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2237-x

Keywords

  • Matrix metalloproteinase-14
  • Non-small cell lung cancer
  • Immunohistochemistry
  • Biomarker
  • Prognosis