Urological Research

, Volume 33, Issue 1, pp 44–50 | Cite as

Matrix metalloproteinases as diagnostic (MMP-13) and prognostic (MMP-2, MMP-9) markers of prostate cancer

  • Giuseppe Morgia
  • Mario Falsaperla
  • Grazia Malaponte
  • Massimo Madonia
  • Manuela Indelicato
  • Salvatore Travali
  • Maria Clorinda Mazzarino
Original Paper


Previous studies have detected high levels of matrix metalloproteinases (MMPs) in metastatic prostate cancer. In this study, we recruited 40 patients with prostate cancer (PCa): 20 presented organ-confined carcinoma and 20 had metastatic cancer. We also recruited 40 subjects for control groups, 20 with benign prostate hyperplasia (BPH) and 20 healthy males with similar characteristics. All of the patients were monitored at the beginning (time 0) and after 90 days. We analyzed the plasma concentrations of MMP-2, MMP-9, MMP-13, TIMP-1 and the enzyme activity of MMP-2 and MMP-9,using specific ELISA tests. The plasma concentrations of MMP-2, MMP-9 and MMP-13 were higher in PCa patients with metastasis than in the other groups, and in these patients decreased markedly after therapy began. For MMP-2 and MMP-9, greater differences were observed in enzyme activity than in plasma concentrations. TIMP-1 was reduced in PCa patients with metastasis, even if the intergroup differences were not statistically significant. Our results suggest that the plasma concentration and activity of MMPs, in association with PSA determination, could play a role in diagnosis, monitoring therapy and evaluating malignant progression in PCa.


Prostate cancer Metalloproteinases Prostate markers 


  1. 1.
    Young TN, Rodriguez GC, Reinhart AR, Bast RCJr, Pizzo SV, Stack M (1996) Characterization of gelatinases linked to extracellular matrix invasion in ovarian adenocarcinoma: purification of matrix metalloproteinase. Gynecol Oncol 62: 89CrossRefPubMedGoogle Scholar
  2. 2.
    Kugler A, Hemmerlein B, Thelen P, Kallerhff M, Radzun H-J, Ringert R-H (1998) Expression of metalloproteinase 2 and 9 and their inhibitors in renal cell carcinoma. J Urol 160: 1914CrossRefPubMedGoogle Scholar
  3. 3.
    Crawford HC, Matrisian LM (1995) Tumor and stromal expression of matrix metalloproteinases and their role in tumor progression. Invasion Metastasis 14: 234Google Scholar
  4. 4.
    Jung K, Novak L, Lein M, Priem F, Schnorr D, Loening SA (1997) Matrix metalloproteinases 1 and 3, tissue inhibitor of metalloproteinasa-1 and the complex of metalloproteinase-1/tissue inhibitor in plasma of patients with prostate cancer. Int J Cancer 74: 220CrossRefPubMedGoogle Scholar
  5. 5.
    Baker T, Tickle S, Wasan H, Docherty A, Isenberg D, Waxam J (1994) Serum metalloproteinases and their inhibitors: markers for malignant potential. Brit J Cancer 70: 506PubMedGoogle Scholar
  6. 6.
    Murray GI, Duncan ME, O’Neil P, Melvin WT, Fothergill E (1996) Matrix metalloproteinase-1 is associated with poor prognosis in colorectal cancer. Nat Med 2: 461PubMedGoogle Scholar
  7. 7.
    Gohji K, Fujimoto N, Fujii A, Komiyama T, Okawa J, Nakajiama M (1996) Prognostic significance of circulating matrix metalloproteinase-2 to tissue inhibitor of metalloproteinase-2 ratio in recurrence of urothelial cancer after complete resection. Cancer Res 56: 3196PubMedGoogle Scholar
  8. 8.
    Kanayama H, Yokota K, Kurokawa Y, Murakami Y, Nishitani M, Kagawa S (1996) Prognostic value of matrix metalloproteinase-2 and tissue inhibitor of metallopreteinase-2 expression in bladder cancer. Cancer Res 56: 3196PubMedGoogle Scholar
  9. 9.
    Lindsay CK, Thorgeiesson UP,Tsuda H, Hirohashi S (1997) Expression of tissue inhibitor of metalloproteinase-1 and type IV collagenase/gelatinase messenger RNAs in human breast cancer. Human Pathol 28: 359Google Scholar
  10. 10.
    Liotta LA, Tryggvason K, Garbisa S, Hart I, Foltz CM, Shafie S (1980) Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature 284: 67PubMedGoogle Scholar
  11. 11.
    Boag AH, Young ID (1994) Increased expression of the 72 kDa type IV collagenase in prostatic adenocarcinoma. Am J.Pathol 144: 585Google Scholar
  12. 12.
    Pendas AM, Uria JA, Jimenez MG, Balbin M, Freije JP, Lopez-Otin C (2000) An overview of collagenase-3 expression in malignant tumors and analysis of its potential value as a target in antitumor therapies. Clin Chim Acta 291: 137CrossRefPubMedGoogle Scholar
  13. 13.
    Wood M, Fudge K , Mohler JL, Frost AR, Garcia F, Wang M, Stearns ME (1997) In situ hybridization studies of metalloproteinases 2 and 9 and TIMP-1 and TIMP-2 expression in human prostate cancer. Clin Exp Metastasis 15: 246CrossRefPubMedGoogle Scholar
  14. 14.
    Oesterling JE, Chan DW, Epstein JI, Kimball AWJr, Bruzek DJ, Rock RC, Brendeer CB, Walsh PC (1998) Prostate specific antigen in the preoperative end postoperative evaluation of localized prostate cancer treated with radical prostatectomy. J Urol 139: 766Google Scholar
  15. 15.
    Hadson MA, Bahnsonn RR, Catalona WJ (1989) Clinical use of prostate specific antigen in patients with prostate cancer. J Urol 142: 1011PubMedGoogle Scholar
  16. 16.
    Catalona WJ, Smith DS, Rathiff TL, Dodds KM, Coplen DE, Yuan JJ, Petros JA, Andriole GL (1991) Measurement of prostate specific antigen in serum as a screening test for prostate cancer. N Engl J Med 324: 1156PubMedGoogle Scholar
  17. 17.
    Glenski WJ, Malek RS, Myrtle JF, Oeslerling JE (1992) Sustained substantially increased concentration of prostate specific antigen in the absence of prostatic malignant disease: an unusual clinical scenario. Mayo Clin Proc 67: 349PubMedGoogle Scholar
  18. 18.
    Chu TM (1998) Prostate specific antigen. In: Sell S (ed) Serological cancer markers. Humana Press, Florence, p 99Google Scholar
  19. 19.
    Albertsen PC (1998) Patologia della prostata nell’anziano: il carcinoma. Minuti 1998: 21Google Scholar
  20. 20.
    Jung K, Nowak L, Lein M, Priem F, Schnorr D, Loening SA (1997) Matrix metalloproteinases 1 and 3, tissue inhibitor of metalloproteinase-1 and the complex of metalloproteinase-1/tissue inhibitor in plasma of patients with prostate cancer. Int J Cancer 74:220CrossRefPubMedGoogle Scholar
  21. 21.
    Moses MA, Wiederschain D, Loughlin KR, Zurakowski D, Lamb CC, Freeman MR (1998) Increased incidence of matrix metalloproteinases in urine of cancer patients. Cancer Res 58: 1395PubMedGoogle Scholar
  22. 22.
    Hamdy FC, Fadlon EJ, Cottam D et al. (1994) Matrix metalloproteinase 9 expression in primary human prostatic adenocarcinoma and benign prostatic hyperplasia. Br J Cancer 69: 177PubMedGoogle Scholar
  23. 23.
    Lichtinghagen R, Musholt PB, Stephan C et al. (2003) mRNA expression profile of matrix metalloproteinases and their tissue inhibitors in malignant and non-malignant prostatic tissue. Anticancer Res 23: 2617PubMedGoogle Scholar
  24. 24.
    Kanoh Y, Akahoshi T, Ohara T et al. (2002) Expression of matrix metalloproteinase-2 and prostate-specific antigen in localized and metastatic prostate cancer. Anticancer Res 22: 1813PubMedGoogle Scholar
  25. 25.
    Lichtinghagen R, Musholt PB, Lein M et al. (2002) Different mRNA and protein expression of matrix metalloproteinases 2 and 9 and tissue inhibitor of metalloproteinases 1 in benign and malignant prostate tissue. Eur Urol 42: 398CrossRefPubMedGoogle Scholar
  26. 26.
    Ross JS, Kaur P, Sheehan CE (2003) Prognostic significance of matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expression in prostate cancer. Mod Pathol 16: 198CrossRefPubMedGoogle Scholar
  27. 27.
    Brehmer B, Biesterfeld S, Jakse G (2003) Expression of matrix metalloproteinases (MMP-2 and -9) and their inhibitors (TIMP-1 and -2) in prostate cancer tissue. Prostate Cancer Prostatic Dis 6: 217CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Giuseppe Morgia
    • 1
  • Mario Falsaperla
    • 1
    • 2
    • 4
  • Grazia Malaponte
    • 3
  • Massimo Madonia
    • 1
  • Manuela Indelicato
    • 3
  • Salvatore Travali
    • 3
  • Maria Clorinda Mazzarino
    • 3
  1. 1.Department of UrologyUniversity of Sassari
  2. 2.Operative Unit of UrologyCentro di Riferimento Oncologico di Basilicata—CROB di Rionero in Vulture
  3. 3.Institute of ImmunologyDepartment of Urology
  4. 4.Via Michele Rigillo snc85028 Rionero in Vulture

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