05Sep 2019

DIAGNOSTIC IMPORTANCE OF MATRIX METALLOPROTEINASE 2 AND 9 AS ADDITIONAL BIOMARKERS IN THE SERA OF BREAST CANCER PATIENTS.

  • Department of Microbiology, Shree M. & N. Virani Science College, YogidhamGurukul, Kalawad Road, Rajkot-360005, Gujarat, India.
  • Department of Pathology, Pramukh Swami Medical College, Karamsad-388325, Gujarat, India.
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Introduction: Tumor invasion and metastasis are the critical steps in breast cancer, leading to detrimental conditions. Matrix metalloproteinase (MMP) 2 and 9 play significant role in progression of breast cancer by degrading type IV collagen. Therefore, the main purpose of the present study was to estimate the concentration of MMP-2 and MMP-9 in the sera of breast cancer patients using zymography and correlate data with existing clinical parameters. Materials & Methods: Sera was collected from 70 breast cancer patients before surgery or who underwent surgery and 50 healthy controls and the activity levels of MMP-2 and MMP-9 were quantified by performing gelatin zymography. Statistical analysis was carried out by using SPSS statistical software (version 20) and Minitab (version 16). Results: The results show that average levels of both MMP-2 and MMP-9 were significantly higher in sera of breast tumor patients as compared to sera of benign breast disease and control group (p<0.001). Additionally, statistical analysis revealed significant direct correlations between levels of both MMPs with different clinical parameters including breast tumor stage, size and tumor grade. Moreover, it was also found that high serum levels of MMP-2 and MMP-9 were associated with lymph node metastasis. Conclusion: Our findings suggest the importance of the detection of serum MMP-2 and MMP-9 as additional biomarkers for the diagnosis of breast cancer and significant clinical use of these enzymes in malignant tumor growth, invasion and metastasis.


  1. Agarwal, G., Ramakant, P. and Forgach, ER. (2009): Breast cancer care in developing countries. World J Surg., 33:2069-76.
  2. Dikshit, R., Gupta, PC.,Ramasundarahettige, C., Gajalakshmi, V., Aleksandrowicz, L., Badwe, R., et al. (2012): Cancer mortality in India: A nationally representative survey. Lancet., 379:1807-16.
  3. Crowe, DL., Tsang, KJ., Shemirani, B. (2001): Jun N-terminal kinase 1 mediates transcriptional induction of matrix metalloproteinase 9 expression. Neoplasia., 3:27?32.
  4. Hanahan, D. and Weinberg RA. (2000): The hallmarks of cancer. Cell.,100: 57-70.
  5. Nagase, H., Visse, R., Murphy, G. (2006): Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res., 69 (3): 562-73.
  6. Garbett, EA., Reed, MWR., Stephenson, TJ., Brown, NJ.(2000): Proteolysis in human breast cancer. J ClinPathol, MolPatho.,53:99-106.
  7. Sternlicht, MD., Coussens, LM., Vu, TH., Werb, Z. (2001): Biology and regulation of the matrix metalloproteinases. In: Appelt K, ed. Matrix metalloproteinase inhibitors in cancer therapy. Totowa, NJ: Humana 1?37.
  8. Nagase, H. (2001): Substrate specificity of MMPs. In: Appelt K, ed. Matrixmetalloproteinase inhibitors in cancer therapy. Totowa, NJ: Humana 39?66.
  9. Zheng-Sheng,Wu., Qiang, Wu., Jiu-Hua, Yang., Hong-Qun, Wang., Xiang-Dong, Ding., Feng, Yang. and Xiao-Chun, Xu. (2008): Prognostic significance of MMP-9 and TIMP-1 serum and tissue expression in breast cancer. J. Cancer., 122: 2050?2056.
  10. Hanemaaijer, R., Verheijen, JH., Maguire, TM., Visser, H., Toet, K., McDermott, E., O?Higgins, N., Duffy, MJ. (2000): Increased gelatinase-A and gelatinase-B activities in malignant vs. benign breast tumors. Int J Cancer., 86:204?7.
  11. Ranuncolo, SM., Armanasco, E., Cresta, C., Joffe, EB., and Puricelli, L. (2003): PlasmaMMP-9 (92-kDA-MMP) activity is useful in the follow-up and in the assessment of prognosis in breast cancer patients. Int J Cancer., 106:745?51.
  12. Jemal, A., Murray, T., Ward, E., Samuels, A., Tiwari, RC.,Ghafoor, A., Feuer, EJ., Thun, MJ. (2005): Cancer statistics 2005. CA Cancer J Clin., 55:10?30.
  13. Duffy, M.J. (2001): Biochemical markers in breast cancer: which ones are clinically useful? ClinBiochem., 34: 347?52.
  14. Arciero, C., Somiari, S., Shriver, C. (2003): Functional relationship and gene ontology classification of breast cancer biomarkers. Int J Biol Markers., 18: 241-72.
  15. King, J., Zhao, J., Clingan, P., Morris, D. (2003): Randomised double blind placebo control study of adjuvant treatment with the metalloproteinase inhibitor, Marimastat in patients with inoperable colorectal hepatic metastases: significant survival advantage in patients with musculoskeletal side-effects. Anticancer Res., 23: 639?645.
  16. Patel, B.P., Shah, S.V., Shukla, S.N., Shah, P.M. and Patel, P.S. (2007): Clinical significance of MMP-2 and MMP-9 in patients with oral cancer. Wiley Inter Science., 29:564-572.
  17. Pucci-Minafra, I., Minafra, S., La Rocca, G., Barranca, M., Fontana, S. and Alaimo, G. (2001): Zymographic analysis of circulating and tissue forms of colon carcinoma gelatinase A (MMP-2) and B (MMP-9) separated by mono- and two-dimensional electrophoresis. Matrix Biol., 20:419?27.
  18. Shah, F.D., Shukla, S.N., Shah, P.M., Shukla, H.K. and Patel, P.S. (2009): Clinical significance of matrix metalloproteinase 2 and 9 in breast cancer. Indian Journal of Cancer., 46 (3): 194-202.
  19. Liu, S.C., Yang, S.F., Yeh, K.T., Yeh, C.M., Chiou, H.L. and Lee C.Y. (2006): Relationship between the level of matrix metalloproteinase-2 and tumor size of breast cancer. ClinChimActa., 371: 92-6.
  20. Schutz, A., Schneidenbach, D., Aust, G., Tannapfel, A., Steinert, M. and Wittekind, C. (2002): Differential expression and activity status of MMP-1, MMP-2 and MMP-9 in tumor and stromal cells of squamous cells carcinoma of the lung. Tumor Biol., 23: 179-84.
  21. Hong, S.D., Hong, S.P., Lee, J.I. and Lim C.Y. (2005): Expression of matrix metalloproteinase-2 and -9 in oral squamous cell carcinoma with regard to the metastatic potential. Oral Oncol., 90: 81-8.
  22. Rocca, G.L., Pucci-Minafra, I., Marrazzo, A., Taormina, P. and Minafra, S. (2004): Zymographic detection and clinical correlations of MMP-2 and MMP-9 in breast cancer sera. British journal of cancer., 90: 1414-1421.
  23. Garbett, E.A., Reed, M.W., Stephenson, T.J. and Brown, N.J. (2000): Proteolysis in human breast cancer. MolPathol., 53: 99-106.
  24. Jezierska, A. and Motyl, T. (2009): Matrix metalloproteinase-2 involvement in breast cancer progression: a mini-review. Med SciMonit., 15: RA32-RA40.
  25. Staack, A., Badendieck, S., Schnorr, D., Loening, S.A. and Jung, K. (2006): Combined determination of plasma MMP2, MMP9, and TIMP1 improves the non-invasive detection of transitional cell carcinoma of the bladder. BMC Urol., 6: 19.
  26. Incorvaia, L., Badalamenti, G., Rini, G., Arcara, C., Fricano, S., Sferrazza, C., Di Trapani, D., Gebbia, N. and Leto, G. (2007): MMP-2, MMP-9 and activinA blood levels in patients with breast cancer or prostate cancer metastasis to the bone. Anticancer Res., 27: 1519-1525.
  27. Jinga, D.C., Blidaru, A., Condrea, I., Ardeleanu, C., Dragomir, C., Szegli, G., Stefanescu, M. and Matache, C. (2006): MMP-9 and MMP-2 gelatinases and TIMP-1 and TIMP-2 inhibitors in breast cancer: correlations with prognostic factors. J Cell Mol Med 2006., 10: 499-510.
  28. Stankovic, C., Konjevic, G., Gopcevic, K., Jovic, V., Inic, M. and Jurisic, V. (2010): Activity of MMP-2 and MMP-9 in sera of breast cancer patients. Pathol Res Pract., 206: 241-247.
  29. Fortunata, V., Fabiana, S., Carolina, M., Tiziana, N., Bruno, V., Mauro, M. and Susanna S. (2013): Plasma levels of matrix metalloproteinases 2 and 9 correlate with histological grade in breast cancer patients. Oncology Letters., 5: 316-320.

[Solanki Sulabhsinh and Shah Menka. (2019); DIAGNOSTIC IMPORTANCE OF MATRIX METALLOPROTEINASE 2 AND 9 AS ADDITIONAL BIOMARKERS IN THE SERA OF BREAST CANCER PATIENTS. Int. J. of Adv. Res. 7 (Sep). 167-177] (ISSN 2320-5407). www.journalijar.com


Solanki Sulabhsinh G.
Department of Microbiology, Shree M. & N. Virani Science College, Yogidham Gurukul, Kalawad Road, Rajkot-360005, Gujarat, India.

DOI:


Article DOI: 10.21474/IJAR01/9644      
DOI URL: http://dx.doi.org/10.21474/IJAR01/9644