Advertisement

Journal of Neuro-Oncology

, Volume 46, Issue 1, pp 81–90 | Cite as

Matrix Metalloproteinase 2 (MMP-2) Immunoreactive Protein is Associated with Poor Grade and Survival in Brain Neoplasms

  • Juha Jäälinojä
  • Riitta Herva
  • Merja Korpela
  • Matti Höyhtyä
  • Taina Turpeenniemi-Hujanen
Article

Abstract

Matrix metalloproteinases play an important role in the invasion of tumor cells and the progression of cancer. The 72 kDa type IV collagenase, a matrix metalloproteinase 2 (MMP-2) has been shown to contribute to the invasion and metastasis in diverse malignant neoplasms.

Object. To elaborate the potential role of MMP-2 in brain tumor invasion we studied the expression and localization of this enzyme protein in 101 brain tumors representing different types of brain neoplasms. For the first time, we also correlated the expression of MMP-2 protein to patient survival.

Methods. Using immunohistochemistry and a monoclonal antibody specific for MMP-2 we found that MMP-2 protein was primarily localized in tumor cells and vasculature cells as well as inflammatory cells. The expression of MMP-2 was absent or negligible in benign tumors (pilocytic astrocytoma and meningioma). Thirty-three percent (6/18) of astrocytomas, 38% (3/8) of anaplastic astrocytomas, 14% (1/7) of anaplastic oligodendrogliomas, 54% (19/35) of glioblastomas and 100% (6/6) of metastatic brain tumors were positive for MMP-2. A correlation between MMP-2 expression and survival was found in malignant brain tumors. The mean survival of patients with an MMP-2 negative tumor was 36 months, when it was only 7–14 months in patients with an MMP-2 positive tumor.

Conclusions. Our data suggest that MMP-2 is associated with histological malignancy and poor survival in brain tumors.

gelatinase A 72 kD type IV collagenase brain tumor invasion prognosis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Birkedal-Hansen H, Moore WGI, Bodden MK, Windsor LJ, Birkedal-Hansen B, DeCarlo A, Engler JA: Matrix metalloproteinases: a review. Crit Rev Oral Biol Med 4: 197-250, 1993Google Scholar
  2. 2.
    Corcoran ML, Hewitt RE, Kiemer DE Jr., Stetler-Stevenson WG: MMP-2: Expression, activation and inhibition. Enzyme Protein 49: 7-19, 1996Google Scholar
  3. 3.
    Strongin AY, Collier I, Bannikov G, Marmer BL, Grant GA, Goldberg GI: Mechanism of cell surface activation of 72-kD type IV collagenase. Isolation of the activated form of membrane metalloproteinase. J BiolChem 270: 5331-5338, 1995Google Scholar
  4. 4.
    Liotta LA, Steeg PS, Stetler-Stevenson WG: Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64: 327-336, 1991Google Scholar
  5. 5.
    Autio-Harmainen H, Karttunen T, Hurskainen T, Höyhtyä M, Kauppila A, Tryggvason K: Expression of 72 kilodalton type IV collagenase (gelatinase A) in benign and malignant ovarian tumors. Lab Invest 69: 312-321, 1993Google Scholar
  6. 6.
    Endo K, Maehara Y, Baba H, Yamamoto M, Tomisaki S, Watanabe A, Kakeji Y, Sugimachi K: Elevated levels of serum and plasma metalloproteinases in patients with gastric cancer. Anticancer Res 17: 2253-2258, 1997Google Scholar
  7. 7.
    Grigioni WF, Garbisa S, D'errico A, Baccarini P, Stetler-Stevenson WG, Liotta LA, Mancini AM: Evaluation of hepatocellular carcinoma aggressiveness by a panel of extracellular matrix antigens. Am J Pathol 138: 647-654, 1991Google Scholar
  8. 8.
    Levy AT, Cioce V, Sobel ME, Garbisa S, Grigioni WF, Liotta LA, Stetler-Stevenson WG: Increased expression of the Mr 72,000 type IV collagenase in human colonic adenocarcinoma. Cancer Res 51: 439-444, 1991Google Scholar
  9. 9.
    Margulies IMK, Höyhtyä M, Evans C, Liotta LA, Stetler-Stevenson WG: Urinary type IV collagenase: elevated levels are associated with bladder transitional cell carcinoma. Cancer Epid Biomark Preven 1: 467-474, 1992Google Scholar
  10. 10.
    Monteguado C, Merino MJ, San-Juan J, Liotta LA, Stetler-Stevenson WG: Immunohistochemical distribution of type IV collagenase in normal, benign, and malignant breast tissue. Am J Pathol 136: 585-592, 1990Google Scholar
  11. 11.
    Pyke C, Ralfkiär E, Huhtala P, Hurskainen T, Danø K, Tryggvason K: Localization of messenger RNA for Mr 72,000 and 92,000 type IV collagenases in human skin cancers by in situ hybridization. Cancer Res 52: 1336-1341, 1992Google Scholar
  12. 12.
    Stearns ME, Wang M: Type IV collagenase (Mr 72,000) expression in human prostate: benign and malignant tissue. Cancer Res 53: 878-883, 1993Google Scholar
  13. 13.
    Urbanski SJ, Edwards DR, Maitland A, Leco KJ, Watson A, Kossakowska AE: Expression of metalloproteinases and their inhibitors in primary pulmonary carcinomas. Br J Cancer 66: 1188-1194, 1992Google Scholar
  14. 14.
    Nakagawa T, Kubota T, Kabuto M, Sato K, Kawano H, Hayakawa T, Okada Y: Production of matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 by human brain tumors. J Neurosurg 81: 69-77, 1994Google Scholar
  15. 15.
    Nakano A, Tani E, Miyazaki K, Yamamoto Y, Furuyama JI: Matrix metalloproteinases and tissue inhibitors of metalloproteinases in human gliomas. J Neurosurg 83: 298-307, 1995Google Scholar
  16. 16.
    Rao JS, Steck PA, Mohanam S, Stetler-Stevenson WG, Liotta LA, Sawaya R: Elevated levels of Mr 92,000 type IV collagenase in human brain tumors. Cancer Res 53: 2208-2211, 1993Google Scholar
  17. 17.
    Rao JS, Yamamoto M, Mohanam S, Gokaslan ZL, Fuller GN, Stetler-Stevenson WG, Rao VH, Liotta LA, Nicolson GL, Sawaya RE: Expression and localisation of 92 kDa type IV collagenase/gelatinaseB(MMP-9) in human gliomas. Clin Exp Metastasis 14: 12-18, 1996Google Scholar
  18. 18.
    Sawaya RE, Yamamoto M, Gokaslan ZL, Wang SW, Mohanam S, Fuller GN, McCutcheon IE, Stetler-Stevenson WG, Nicolson GL, Rao JS: Expression and localisation of 72 kDa type IV collagenase (MMP-2) in human malignant gliomas in vivo. Clin Exp Metastasis 14: 35-42, 1996Google Scholar
  19. 19.
    Saxena A, Robertson JT, Kufta C, Stetler-Stevenson WG, Ali IU: Increased expression of gelatinase A and TIMP-2 in primary human glioblastomas. Int J Oncol 7: 469-473, 1995Google Scholar
  20. 20.
    Garzetti GG, Ciavattini A, Lucarini G, Goteri G, deNictolis M, Garbisa S, Masiero L, Romanini C, Graziella B: Tissue and serum metalloproteinase (MMP-2) expression in advanced ovarian serous cystadenocarcinomas: clinical and prognostic implications. Anticancer Res 15: 2799-2804, 1995Google Scholar
  21. 21.
    Gohji K, Fujimoto N, Komiyama T, Fujii A, Ohkawa J, Kamidono S, Nakajima M: Elevation of serum levels of matrix metalloproteinase-2 and-3 as new predictors of recurrence in patients with urothelial carcinoma. Cancer 78: 2379-2387, 1996Google Scholar
  22. 22.
    Talvensaari-Mattila A, Pääkkö P, Höyhtyä M, Blanco-Sequeiros G, Turpeenniemi-Hujanen T: Matrix metalloproteinase-2 immunoreactive protein: a marker of aggressiveness in breast carcinoma. Cancer 83: 1153-1162, 1998Google Scholar
  23. 23.
    Väisänen A, Kallioinen M, Taskinen PJ, Turpeenniemi-Hujanen T: Prognostic value of MMP-2 immunoreactive protein (72 kD type IV collagenase) in primary skin melanoma. J Pathol 186: 51-58, 1998Google Scholar
  24. 24.
    Bjerkvig R, Lund-Johansen M, Edvardsen K: Tumor cell invasion and angiogenesis in the central nervous system. Curr Opin Oncol 9: 223-229, 1997Google Scholar
  25. 25.
    Stemmer-Rachamimov AO, Louis DN: Histopathologic and immunohistochemical prognostic factors in malignant gliomas. Curr Opin Oncol 9: 230-234, 1997Google Scholar
  26. 26.
    Kleihues P, Burger PC, Scheithauer BW: Histological typing of tumours of the central nervous system. World Health Organization. In: International Histological Classification of Tumours. 2nd edn., Springer-Verlag, Berlin, Heidelberg, 1993Google Scholar
  27. 27.
    Hsu SM, Raine L, Fanger H: Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29: 557-580, 1981Google Scholar
  28. 28.
    Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457-481, 1958Google Scholar
  29. 29.
    Mantel N: Evaluation of survival data and two new rank order statistics arising in this consideration. Cancer Chemother Rep 50: 163-170, 1966Google Scholar
  30. 30.
    Paganetti PA, Caroni P, Schwab MB: Glioblastoma infiltration into central nervous system tissue in vitro: involvement of a metalloprotease. J Cell Biol 107: 2281-2291, 1988Google Scholar
  31. 31.
    Abe T, Mori T, Kohno K, Seiki M, Hayakawa T, Welgus HG, Hori S, Kuwano M: Expresion of 72 kDa type IV collagenase and invasion activity of human glioma cells. Clin Exp Metastasis 12: 296-304, 1994Google Scholar
  32. 32.
    Boghaert ER, Chan SK, Zimmer C, Grobelny D, Galardy RE, Vanaman TC, Zimmer SG: Inhibition of collagenolytic activity relates to quantitative reduction of invasion in vitro in a c-Ha-ras transfected glial cell line. J Neuro-Oncol 21: 141-150, 1994Google Scholar
  33. 33.
    Lund-Johansen M, Rucklidge GJ, Milne G, Bjerkvig R: A metalloproteinase, capable of destroying cultured brain tissue isolated from rat glioma cells. Anticancer Res 11: 1001-1006, 1991Google Scholar
  34. 34.
    Nakagawa T, Kubota T, Kabuto M, Fujimoto N, Okada Y: Secretion of MMP-2 by malignant human glioma cell lines: implications for the growth and cellular invasion of the extracellular matrix. J Neuro-Oncol 28: 13-24, 1996Google Scholar
  35. 35.
    Rao JS, Steck PA, Tofilon P, Boyd D, Ali-Osman F, Stetler-Stevenson WG, Liotta LA, Sawaya R: Role of plasminogen activator and of 92-kDa type IV collagenase in glioblastoma invasion using an in vitro matrigel model. J Neuro-Oncol 18: 129-138, 1994Google Scholar
  36. 36.
    Rutka JT, Matsuzawa K, Hubbard SL, Fukuyama K, Becker LE, Stetler-Stevenson WG, Edwards DR, Dirks PB: Expression of TIMP-1, TIMP-2, 72-and 92-kDa type IV collagenase transcripts in human astrocytoma cell lines: correlation with astrocytoma cell line invasiveness. Int J Oncol 6: 877-884, 1995Google Scholar
  37. 37.
    Halaka AN, Bunning RAD, Bird CC, Gibson M, Reynolds JJ: Production of collagenase and inhibitor (TIMP) by intracranial tumors and dura in vitro. J Neurosurg 59: 461-466, 1983Google Scholar
  38. 38.
    Mohanam S, Wang SW, Rayford A, Yamamoto M, Sawaya R, Nakajima M, Liotta LA, Nicolson GL, Stetler-Stevenson WG, Rao JS: Expression of tissue inhibitors of metalloproteinases: negative regulators of human glioblastoma invasion in vivo. Clin Exp Metastasis 13: 57-62, 1995Google Scholar
  39. 39.
    Ring P, Johansson K, Höyhtyä M, Rubin K, Lindmark G: Expression of tissue inhibitor of metalloproteinases TIMP-2 in human colorectal cancer-a predictor of tumour stage. Br J Cancer 76: 805-811, 1997Google Scholar
  40. 40.
    Russel DS, Rubinstein LJ: Pathology of Tumours of the Nervous System. London, Edward Arnold, edn., 5, 1989Google Scholar
  41. 41.
    Apodaca G, Rutka JT, Bouhana K, Berens ME, Giblin JR, Rosenblum ML, McKerrow JH, Banda MJ: Expression of metalloproteinases and metalloproteinase inhibitors by fetal astrocytes and glioma cell lines. Cancer Res 50: 2322-2329, 1990Google Scholar
  42. 42.
    DeClerck YA, Shimada H, Gonzalez-Gomez I, Raffel C: Tumoral invasion in the central nervous system. J Neuro-Oncol 18: 111-121, 1994Google Scholar
  43. 43.
    Laerum OD, Bjerkvig R, Steinsvåg SK, de Ridder L: Invasiveness of primary brain tumors. Cancer Metastasis Rev 3: 223-236, 1984Google Scholar
  44. 44.
    Bindal AK, Hammoud M, Shi WM, Wu SZ, Sawaya R, Rao JS: Prognostic significance of proteolytic enzymes in human brain tumors. J Neuro-Oncol 22: 101-110, 1994Google Scholar
  45. 45.
    Reith A, Rucklidge GJ: Invasion of brain tissue by primary glioma: evidence for the involvement of urokinase-type plasminogen activator as an activator of type IV collagenase. Biochem Biophys Res Commun 186: 348-354, 1992Google Scholar
  46. 46.
    Mignatti P, Robbins E, Rifkin DB: Tumor invasion through the amniotic membrane: requirement for a proteinase cascade. Cell 47: 487-498, 1986Google Scholar
  47. 47.
    Leon SP, Folkerth RD, Black PML: Microvessel density is a prognostic indicator for patients with astroglial brain tumors. Cancer 77: 362-372, 1996Google Scholar
  48. 48.
    Abdulrauf SI, Edvardsen K, Ho KL, Yang XY, Rock PJ, Rosenblum ML: Vascular endothelial growth factor expression and vascular density as prognostic markers of survival in patients with low-grade astrocytoma. J Neurosurg 88: 513-520, 1998Google Scholar
  49. 49.
    Folkman J: What is the evidence that tumors are angiogenesis-dependent? JNCI 82: 4-6, 1990Google Scholar
  50. 50.
    Davies B, Brown PD, East N, Crimmin MJ, Balkwill FR: A synthetic matrix metalloproteinase inhibitor decreases tumor burden and prolongs survival of mice bearing human ovarian carcinoma xenografts. Cancer Res 53: 2087-2091, 1993Google Scholar
  51. 51.
    Taraboletti G, Garofalo A, Belotti D, Drudis T, Borsotti P, Scanziani E, Brown PD, Giavazzi R: Inhibition of angiogenesis and murine hemangioma growth by Batimastat, a synthetic inhibitor of matrix metalloproteinases. JNCI 87: 294-298, 1995Google Scholar
  52. 52.
    Murphy AN, Unsworth EJ, Stetler-Stevenson WG: Tissue inhibitor of metalloproteinases-2 inhibits bFGF-induced human microvascular endothelial cell proliferation. J Cell Physiol 157: 351-358, 1993Google Scholar
  53. 53.
    Takigawa M, Nishida Y, Suzuki F, Kishi JI, Yamashita K, Hayaka T: Induction of angiogenesis in chick yolk-sac membrane by polyamines and its inhibition by tissue inhibitors of metalloproteinases (TIMP and TIMP-2) Biochem Biophys Res Commun 171: 1264-1271, 1990Google Scholar

Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Juha Jäälinojä
    • 1
  • Riitta Herva
    • 2
  • Merja Korpela
    • 1
  • Matti Höyhtyä
    • 3
  • Taina Turpeenniemi-Hujanen
    • 1
  1. 1.Department of Oncology and RadiotherapyUniversity of Oulu, Oulu University Hospital, KajaanintieOuluFinland
  2. 2.Department of PathologyUniversity of Oulu, Oulu University Hospital, KajaanintieOuluFinland
  3. 3.Diabor Ltd., KiviharjuntieOuluFinland

Personalised recommendations