Tumor Biology

, Volume 35, Issue 11, pp 11647–11653 | Cite as

EMMPRIN and ADAM12 in prostate cancer: preliminary results of a prospective study

  • Elif Bilgin Doğru
  • Yavuz Dizdar
  • Ece Akşit
  • Feyyaz Ural
  • Öner Şanlı
  • Vildan Yasasever
Research Article


Extracellular metalloproteinase inducer (EMMPRIN) and a disintegrin and metalloproteinase (ADAM12) play a major role in cancer invasion and metastasis owing to the fact that they are directly related to the cell microenvironment and extracellular matrix (ECM) degradation. The aim of this study was to search for an answer to the question “whether the determination of EMMPRIN and ADAM12 values especially in urine may be helpful for the early diagnosis of prostate cancer without employing invasive methods” and also to check whether they may be useful for the determination of the patients with high metastasis risk. Peripheral blood and urine from 66 prostate cancer patients (40 local, 20 locally advanced, 6 metastatic) and 14 healthy controls were evaluated by enzyme-linked immunosorbent assay (ELISA) method. Serum EMMPRIN and ADAM12 values of the patients were seen to be statistically higher than the serum EMMPRIN and ADAM12 values of the healthy controls (p = 0.01 and p = 0.001, respectively). The urine ADAM12 levels were significantly higher in patients (p = 0.013). No significant relationships were found between urine EMMPRIN values of the patients and the healthy controls (p > 0.05). Positive correlation between urine EMMPRIN–urine ADAM12 tests was found in total patients group (r = 0.683, p = 0.001). Our preliminary results revealed that serum EMMPRIN and ADAM12 values and urine ADAM12 values may be useful markers in prostate cancer therapy. Due to the high correlation between these two tests, we are of the opinion that the use of urine ADAM12 in clinic may be sufficient and favorable together with prostate-specific antigen (PSA) for treatment.


Prostate Cancer Matrix metalloproteinase EMMPRIN ADAM12 



The present work was supported by the Research Fund of Istanbul University, Project No. 18287.

Conflicts of interest



  1. 1.
    Van Hoorde L, Van Aken E, Mareel M. Collagen type I: a substrate and a signal for invasion. Prog Mol Subcell Biol. 2000;25:105–34.PubMedCrossRefGoogle Scholar
  2. 2.
    Aksun SA, Özmen D, Bayındır O. Metalloproteinazlar, inhibitörleri ve ilişkili fizyolojik ve patolojik durumlar. Turk Klin J Med Sci. 2001;21:332–42.Google Scholar
  3. 3.
    Reel B. Matriks metalloproteinaz enzimleri ve ateroskleroz. Turk Klin J Med Sci. 2006;26:527–37.Google Scholar
  4. 4.
    van Hinsbergh VWM, Engelse MA, Quax PH. Pericellular proteases in angiogenesis and vasculogenesis. Arterioscler Thromb Vasc Biol. 2006;26:716–28.PubMedCrossRefGoogle Scholar
  5. 5.
    Roy R, Yang J, Moses MA. Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. J Clin Oncol. 2009;27:5287–97.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Riethdorf S, Reimers N, Assmann V, Kornfeld JW, Terracciano L, Sauter G, et al. High incidence of EMMPRIN in human tumors. Int J Cancer. 2006;119:1800–10.PubMedCrossRefGoogle Scholar
  7. 7.
    Biswas C. Tumor cell stimulation of collagenase production by fibroblasts. Biochem Biophys Res Commun. 1982;109:1026–34.PubMedCrossRefGoogle Scholar
  8. 8.
    Biswas C, Zhang Y, DeCastro R, Guo H, Nakamura T, Kataoka H, et al. The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily. Cancer Res. 1995;55:434–9.PubMedGoogle Scholar
  9. 9.
    Tang Y, Nakada MT, Kesavan P, McCabe F, Millar H, Rafferty P, et al. Extracellular matrix metalloproteinase ınducer stimulates tumor angiogenesis by elevating vascular endothelial growth factor and matrix metalloproteinases. Cancer Res. 2005;65:3193–9.PubMedGoogle Scholar
  10. 10.
    Bougatef F, Quemener C, Kellouche S, Naïmi B, Podgorniak MP, Millot G, et al. EMMPRIN promotes angiogenesis through hypoxia-inducible factor-2alpha-mediated regulation of soluble VEGF isoforms and their receptor VEGFR-2. Blood. 2009;114:5547–56.PubMedCrossRefGoogle Scholar
  11. 11.
    Huovila AP, Turner AJ, Pelto-Huikko M, Karkkainen I, Ortiz RM. Shedding light on ADAM metalloproteinases. Trends Biochem Sci. 2005;30:413–22.PubMedCrossRefGoogle Scholar
  12. 12.
    Wolfsberg TG, White JM. ADAM metalloproteases. In: Barrett AJ, Rawlings ND, Woessner JF, editors. Handbook of proteolytic enzymes. London: Academic; 2003. p. 1310–3.Google Scholar
  13. 13.
    Reiss K, Saftig P. The “A Disintegrin And Metalloprotease” (ADAM) family of sheddases: physiological and cellular functions. Semin Cell Dev Biol. 2009;20:126–37.PubMedCrossRefGoogle Scholar
  14. 14.
    Kumar RJ, Barqawi AB, Crawford ED. Epidemiology of prostate cancer. US Oncol Rev. 2005;1:1–6.Google Scholar
  15. 15.
    Tosoian J, Loeb S. PSA and beyond: the past, present, and future of investigative biomarkers for prostate cancer. Sci World J. 2010;10:1919–31.CrossRefGoogle Scholar
  16. 16.
    Verrier S, Hogan A, McKie N, Horton M. ADAM gene expression and regulation during human osteoclast formation. Bone. 2004;35:34–46.PubMedCrossRefGoogle Scholar
  17. 17.
    Georges S, Chesneau J, Hervouet S, Taurelle J, Gouin F, Redini F, et al. A disintegrin and metalloproteinase 12 produced by tumour cells accelerates osteosarcoma tumour progression and associated osteolysis. Eur J Cancer. 2013;49:2253–63.PubMedCrossRefGoogle Scholar
  18. 18.
    Roy R, Wewer UM, Zurakowski D, Pories SE, Moses MA. ADAM 12 cleaves extracellular matrix proteins and correlates with cancer status and stage. J Biol Chem. 2004;279:51323–30.PubMedCrossRefGoogle Scholar
  19. 19.
    Roy R, Rodig S, Bielenberg D, Zurakowski D, Moses MA. ADAM12 transmambrane and secreted isoforms promote breast tumor growth: a distinct role for ADAM12-S protein in tumor metastasis. J Biol Chem. 2011;286:20758–68.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Pories SE, Zurakowski D, Roy R, Lamb CC, Raza S, Exarhopoulos A, et al. Urinary metalloproteinases: noninvasive biomarkers for breast cancer risk assessment. Cancer Epidemiol Biomarkers Prev. 2008;17:1034–42.PubMedCrossRefGoogle Scholar
  21. 21.
    Sanli O, Acar O, Celtik M, Oktar T, Kilicaraslan I, Ozcan F, et al. Should prostate cancer status be determined in patients undergoing radical cystoprostatectomy? Urol Int. 2006;77:307–10.PubMedCrossRefGoogle Scholar
  22. 22.
    Fröhlich C, Albrechtsen R, Dyrskjøt L, Rudkjaer L, Ørntoft TF, Wewer UM. Molecular profiling of ADAM12 in human bladder cancer. Clin Cancer Res. 2006;12:7359–68.PubMedCrossRefGoogle Scholar
  23. 23.
    Peduto L, Reuter VE, Sehara-Fujisawa A, Shaffer DR, Scher HI, Blobel CP. ADAM12 is highly expressed in carcinoma-associated stroma and is required for mouse prostate tumor progression. Oncogene. 2006;25:5462–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Han ZD, He HC, Bi XC, Qin WJ, Dai QS, Zou J, et al. Expression and clinical significance of CD147 in genitourinary carcinomas. J Surg Res. 2010;160:260–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Bi XC, Liu JM, Zheng XG, Xian ZY, Feng ZW, Lou YX, et al. Over-expression of extracellular matrix metalloproteinase inducer in prostate cancer is associated with high risk of prostate-specific antigen relapse after radical prostatectomy. Clin Invest Med. 2011;34:358.Google Scholar
  26. 26.
    Zhong WD, Liang YX, Lin SX, Li L, He HC, Bi XC, et al. Expression of CD147 is associated with prostate cancer progression. Int J Cancer. 2012;130:300–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Zhu H, Zhao J, Zhu B, Collazo J, Gal J, Shi P, et al. EMMPRIN regulates cytoskeleton reorganization and cell adhesion in prostate cancer. Prostate. 2012;72:72–81.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Han ZD, Bi XC, Qin WJ, He HC, Dai QS, Zou J, et al. CD147 expression indicates unfavourable prognosis in prostate cancer. Pathol Oncol Res. 2009;15:369–74.PubMedCrossRefGoogle Scholar
  29. 29.
    Zhong WD, Han ZD, He HC, Bi XC, Dai QS, Zhu G, et al. CD147, MMP-1, MMP-2 and MMP-9 protein expression as significant prognostic factors in human prostate cancer. Oncology. 2008;75:230–6.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Elif Bilgin Doğru
    • 1
  • Yavuz Dizdar
    • 2
  • Ece Akşit
    • 1
  • Feyyaz Ural
    • 3
  • Öner Şanlı
    • 3
  • Vildan Yasasever
    • 1
  1. 1.Basic Oncology Department, Institute of OncologyUniversity of IstanbulIstanbulTurkey
  2. 2.Clinical Oncology Department, Institute of OncologyUniversity of IstanbulIstanbulTurkey
  3. 3.Department of Urology, Faculty of MedicineUniversity of IstanbulIstanbulTurkey

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