Skip to main content
Top
Published in: Virchows Archiv 6/2004

01-06-2004 | Original Article

Expression and activity of matrix metalloproteinases-2 and -9 in serum, core needle biopsies and tissue specimens of prostate cancer patients

Authors: Christian G. Sauer, Alexandra Kappeler, Monika Späth, Jens J. Kaden, Maurice S. Michel, Doris Mayer, Uwe Bleyl, Rainer Grobholz

Published in: Virchows Archiv | Issue 6/2004

Login to get access

Abstract

Prostate cancer is the most common cancer in men and second in the cancer-related frequency of mortality. Matrix metalloproteinases (MMPs) are involved in tumor invasion and metastasis in various malignancies. MMP-2 and MMP-9 are capable of digesting collagen type IV. Numerous studies have demonstrated an association between increased MMP-2 and -9 expression and tumor progression in various tumors. In this study, the expression and activities of MMP-2 and -9 were assessed in serum probes and tumor tissue from core needle biopsies and radical prostatectomies of 97 patients. MMP-2 and -9 serum expression was analyzed in a subgroup of 31 patients. MMP-9 serum expression was significantly increased in tumor patients and correlated with tumor grade. In contrast, the MMP-9 tissue expression and activity revealed no significant correlations to tumor stage or grade. The MMP-2 activity, however, showed a positive correlation for MMP-2 with tumor stage. Increased activity was predominantly detected in advanced tumor stages. Immunohistochemical analysis of MMP-2 expression demonstrated a positive association with tumor grade in prostatectomy specimens. The relative expression rates in biopsies matched in 65% with those of the prostatectomies. Detection of MMP-2 in core needle biopsies seems not to be a helpful marker for diagnostic purposes.
Literature
1.
go back to reference Birkedal-Hansen H (1995) Proteolytic remodeling of extracellular matrix. Curr Opin Cell Biol 7:728–735PubMed Birkedal-Hansen H (1995) Proteolytic remodeling of extracellular matrix. Curr Opin Cell Biol 7:728–735PubMed
2.
go back to reference Boag AH, Young ID (1993) Immunohistochemical analysis of type IV collagenase expression in prostatic hyperplasia and adenocarcinoma. Mod Pathol 6:65–68PubMed Boag AH, Young ID (1993) Immunohistochemical analysis of type IV collagenase expression in prostatic hyperplasia and adenocarcinoma. Mod Pathol 6:65–68PubMed
3.
go back to reference Curran S, Murray GI (1999) Matrix metalloproteinases in tumour invasion and metastasis. J Pathol 189:300–308CrossRefPubMed Curran S, Murray GI (1999) Matrix metalloproteinases in tumour invasion and metastasis. J Pathol 189:300–308CrossRefPubMed
4.
go back to reference Davies B, Miles DW, Happerfield LC, Naylor MS, Bobrow LG, Rubens RD, Balkwill FR (1993) Activity of type IV collagenases in benign and malignant breast disease. Br J Cancer 67:1126–1131PubMed Davies B, Miles DW, Happerfield LC, Naylor MS, Bobrow LG, Rubens RD, Balkwill FR (1993) Activity of type IV collagenases in benign and malignant breast disease. Br J Cancer 67:1126–1131PubMed
5.
go back to reference Festuccia C, Bologna M, Vicentini C, Tacconelli A, Miano R, Violini S, Mackay AR (1996) Increased matrix metalloproteinase-9 secretion in short-term tissue cultures of prostatic tumor cells. Int J Cancer 69:386–393CrossRefPubMed Festuccia C, Bologna M, Vicentini C, Tacconelli A, Miano R, Violini S, Mackay AR (1996) Increased matrix metalloproteinase-9 secretion in short-term tissue cultures of prostatic tumor cells. Int J Cancer 69:386–393CrossRefPubMed
6.
go back to reference Giannelli G, Fransvea E, Marinosci F, Bergamini C, Daniele A, Colucci S, Paradiso A, Quaranta M, Antonaci S (2002) Gelatinase levels in male and female breast cancer. Biochem Biophys Res Commun 292:161–166CrossRefPubMed Giannelli G, Fransvea E, Marinosci F, Bergamini C, Daniele A, Colucci S, Paradiso A, Quaranta M, Antonaci S (2002) Gelatinase levels in male and female breast cancer. Biochem Biophys Res Commun 292:161–166CrossRefPubMed
7.
go back to reference Gleason DF (1992) Histologic grading of prostate cancer: a perspective. Hum Pathol 23:273–279PubMed Gleason DF (1992) Histologic grading of prostate cancer: a perspective. Hum Pathol 23:273–279PubMed
8.
go back to reference Gohji K, Fujimoto N, Hara I, Fujii A, Gotoh A, Okada H, Arakawa S, Kitazawa S, Miyake H, Kamidono S (1998) Serum matrix metalloproteinase-2 and its density in men with prostate cancer as a new predictor of disease extension. Int J Cancer 79:96–101CrossRefPubMed Gohji K, Fujimoto N, Hara I, Fujii A, Gotoh A, Okada H, Arakawa S, Kitazawa S, Miyake H, Kamidono S (1998) Serum matrix metalloproteinase-2 and its density in men with prostate cancer as a new predictor of disease extension. Int J Cancer 79:96–101CrossRefPubMed
9.
go back to reference Hamdy FC, Fadlon EJ, Cottam D, Lawry J, Thurrell W, Silcocks PB, Anderson JB, Williams JL, Rees RC (1994) Matrix metalloproteinase 9 expression in primary human prostatic adenocarcinoma and benign prostatic hyperplasia. Br J Cancer 69:177–182PubMed Hamdy FC, Fadlon EJ, Cottam D, Lawry J, Thurrell W, Silcocks PB, Anderson JB, Williams JL, Rees RC (1994) Matrix metalloproteinase 9 expression in primary human prostatic adenocarcinoma and benign prostatic hyperplasia. Br J Cancer 69:177–182PubMed
10.
go back to reference Ishimaru H, Kageyama Y, Hayashi T, Nemoto T, Eishi Y, Kihara K (2002) Expression of matrix metalloproteinase-9 and bombesin/gastrin-releasing peptide in human prostate cancers and their lymph node metastases. Acta Oncol 41:289–296CrossRefPubMed Ishimaru H, Kageyama Y, Hayashi T, Nemoto T, Eishi Y, Kihara K (2002) Expression of matrix metalloproteinase-9 and bombesin/gastrin-releasing peptide in human prostate cancers and their lymph node metastases. Acta Oncol 41:289–296CrossRefPubMed
11.
go back to reference Jemal A, Thomas A, Murray T, Thun M (2002) Cancer statistics, 2002. CA Cancer J Clin 52:23–47PubMed Jemal A, Thomas A, Murray T, Thun M (2002) Cancer statistics, 2002. CA Cancer J Clin 52:23–47PubMed
12.
go back to reference Jung K, Laube C, Lein M, Lichtinghagen R, Tschesche H, Schnorr D, Loening SA (1998) Kind of sample as preanalytical determinant of matrix metalloproteinase 2 and 9 and tissue inhibitor of metalloproteinase 2 in blood. Clin Chem 44:1060–1062PubMed Jung K, Laube C, Lein M, Lichtinghagen R, Tschesche H, Schnorr D, Loening SA (1998) Kind of sample as preanalytical determinant of matrix metalloproteinase 2 and 9 and tissue inhibitor of metalloproteinase 2 in blood. Clin Chem 44:1060–1062PubMed
13.
go back to reference Jung K, Laube C, Lein M, Turk I, Lichtinghagen R, Rudolph B, Schnorr D, Loening SA (1998) Matrix metalloproteinase-2 in blood does not indicate the progression of prostate cancer. Int J Cancer 78:392–393CrossRefPubMed Jung K, Laube C, Lein M, Turk I, Lichtinghagen R, Rudolph B, Schnorr D, Loening SA (1998) Matrix metalloproteinase-2 in blood does not indicate the progression of prostate cancer. Int J Cancer 78:392–393CrossRefPubMed
14.
go back to reference Kanoh Y, Akahoshi T, Ohara T, Ohtani N, Mashiko T, Ohtani S, Egawa S, Baba S (2002) Expression of matrix metalloproteinase-2 and prostate-specific antigen in localized and metastatic prostate cancer. Anticancer Res 22:1813–1817PubMed Kanoh Y, Akahoshi T, Ohara T, Ohtani N, Mashiko T, Ohtani S, Egawa S, Baba S (2002) Expression of matrix metalloproteinase-2 and prostate-specific antigen in localized and metastatic prostate cancer. Anticancer Res 22:1813–1817PubMed
15.
go back to reference Kawano N, Osawa H, Ito T, Nagashima Y, Hirahara F, Inayama Y, Nakatani Y, Kimura S, Kitajima H, Koshikawa N (1997) Expression of gelatinase A, tissue inhibitor of metalloproteinases-2, matrilysin, and trypsin(ogen) in lung neoplasms: an immunohistochemical study. Hum Pathol 28:613–622PubMed Kawano N, Osawa H, Ito T, Nagashima Y, Hirahara F, Inayama Y, Nakatani Y, Kimura S, Kitajima H, Koshikawa N (1997) Expression of gelatinase A, tissue inhibitor of metalloproteinases-2, matrilysin, and trypsin(ogen) in lung neoplasms: an immunohistochemical study. Hum Pathol 28:613–622PubMed
16.
go back to reference Knauper V, Will H, Lopez-Otin C, Smith B, Atkinson SJ, Stanton H, Hembry RM, Murphy G (1996) Cellular mechanisms for human procollagenase-3 (MMP-13) activation. Evidence that MT1-MMP (MMP-14) and gelatinase a (MMP-2) are able to generate active enzyme. J Biol Chem 271:17124–17131PubMed Knauper V, Will H, Lopez-Otin C, Smith B, Atkinson SJ, Stanton H, Hembry RM, Murphy G (1996) Cellular mechanisms for human procollagenase-3 (MMP-13) activation. Evidence that MT1-MMP (MMP-14) and gelatinase a (MMP-2) are able to generate active enzyme. J Biol Chem 271:17124–17131PubMed
17.
go back to reference Knauper V, Smith B, Lopez-Otin C, Murphy G (1997) Activation of progelatinase B (proMMP-9) by active collagenase-3 (MMP-13). Eur J Biochem 248:369–373PubMed Knauper V, Smith B, Lopez-Otin C, Murphy G (1997) Activation of progelatinase B (proMMP-9) by active collagenase-3 (MMP-13). Eur J Biochem 248:369–373PubMed
18.
go back to reference Lehti K, Lohi J, Valtanen H, Keski-Oja J (1998) Proteolytic processing of membrane-type-1 matrix metalloproteinase is associated with gelatinase A activation at the cell surface. Biochem J 334:345–353PubMed Lehti K, Lohi J, Valtanen H, Keski-Oja J (1998) Proteolytic processing of membrane-type-1 matrix metalloproteinase is associated with gelatinase A activation at the cell surface. Biochem J 334:345–353PubMed
19.
go back to reference Liabakk NB, Talbot I, Smith RA, Wilkinson K, Balkwill F (1996) Matrix metalloprotease 2 (MMP-2) and matrix metalloprotease 9 (MMP-9) type IV collagenases in colorectal cancer. Cancer Res 56:190–196 Liabakk NB, Talbot I, Smith RA, Wilkinson K, Balkwill F (1996) Matrix metalloprotease 2 (MMP-2) and matrix metalloprotease 9 (MMP-9) type IV collagenases in colorectal cancer. Cancer Res 56:190–196
20.
go back to reference Lichtinghagen R, Musholt P, Lein M, Romer A, Rudolph B, Kristiansen G, Hauptmann S, Schnorr D, Loening S, Jung K (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 42:398–406CrossRefPubMed Lichtinghagen R, Musholt P, Lein M, Romer A, Rudolph B, Kristiansen G, Hauptmann S, Schnorr D, Loening S, Jung K (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 42:398–406CrossRefPubMed
21.
go back to reference Lokeshwar BL, Selzer MG, Block NL, Gunja-Smith Z (1993) Secretion of matrix metalloproteinases and their inhibitors (tissue inhibitor of metalloproteinases) by human prostate in explant cultures: reduced tissue inhibitor of metalloproteinase secretion by malignant tissues. Cancer Res 53:4493–4498 Lokeshwar BL, Selzer MG, Block NL, Gunja-Smith Z (1993) Secretion of matrix metalloproteinases and their inhibitors (tissue inhibitor of metalloproteinases) by human prostate in explant cultures: reduced tissue inhibitor of metalloproteinase secretion by malignant tissues. Cancer Res 53:4493–4498
22.
go back to reference Matrisian LM (1990) Metalloproteinases and their inhibitors in matrix remodeling. Trends Genet 6:121–125PubMed Matrisian LM (1990) Metalloproteinases and their inhibitors in matrix remodeling. Trends Genet 6:121–125PubMed
23.
go back to reference Montironi R, Lucarini G, Castaldini C, Galluzzi CM, Biagini G, Fabris G (1996) Immunohistochemical evaluation of type IV collagenase (72-kd metalloproteinase) in prostatic intraepithelial neoplasia. Anticancer Res 16:2057–2062PubMed Montironi R, Lucarini G, Castaldini C, Galluzzi CM, Biagini G, Fabris G (1996) Immunohistochemical evaluation of type IV collagenase (72-kd metalloproteinase) in prostatic intraepithelial neoplasia. Anticancer Res 16:2057–2062PubMed
24.
go back to reference Nagase H, Woessner JF Jr (1999) Matrix metalloproteinases. J Biol Chem 274:21491–21494PubMed Nagase H, Woessner JF Jr (1999) Matrix metalloproteinases. J Biol Chem 274:21491–21494PubMed
25.
go back to reference Nawrocki B, Polette M, Marchand V, Monteau M, Gillery P, Tournier JM, Birembaut P (1997) Expression of matrix metalloproteinases and their inhibitors in human bronchopulmonary carcinomas: quantificative and morphological analyses. Int J Cancer 72:556–564CrossRefPubMed Nawrocki B, Polette M, Marchand V, Monteau M, Gillery P, Tournier JM, Birembaut P (1997) Expression of matrix metalloproteinases and their inhibitors in human bronchopulmonary carcinomas: quantificative and morphological analyses. Int J Cancer 72:556–564CrossRefPubMed
26.
go back to reference Ross JS, Kaur P, Sheehan CE, Fisher HA, Kaufman RA Jr, Kallakury BV (2003) Prognostic significance of matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expression in prostate cancer. Mod Pathol 16:198–205PubMed Ross JS, Kaur P, Sheehan CE, Fisher HA, Kaufman RA Jr, Kallakury BV (2003) Prognostic significance of matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expression in prostate cancer. Mod Pathol 16:198–205PubMed
27.
go back to reference Sato H, Takino T, Okada Y, Cao J, Shinagawa A, Yamamoto E, Seiki M (1994) A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature 370:61–65PubMed Sato H, Takino T, Okada Y, Cao J, Shinagawa A, Yamamoto E, Seiki M (1994) A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature 370:61–65PubMed
28.
go back to reference Sobin LH, Wittekind CH (eds) (1997) TNM classification of malignant tumours, 5th edn. Wiley-Liss Inc., New York Sobin LH, Wittekind CH (eds) (1997) TNM classification of malignant tumours, 5th edn. Wiley-Liss Inc., New York
29.
go back to reference Stearns M, Stearns ME (1996) Evidence for increased activated metalloproteinase 2 (MMP-2a) expression associated with human prostate cancer progression. Oncol Res 8:69–75 Stearns M, Stearns ME (1996) Evidence for increased activated metalloproteinase 2 (MMP-2a) expression associated with human prostate cancer progression. Oncol Res 8:69–75
30.
go back to reference Trudel D, Fradet Y, Meyer F, Harel F, Tetu B (2003) Significance of MMP-2 expression in prostate cancer: an immunohistochemical study. Cancer Res 63:8511–8515PubMed Trudel D, Fradet Y, Meyer F, Harel F, Tetu B (2003) Significance of MMP-2 expression in prostate cancer: an immunohistochemical study. Cancer Res 63:8511–8515PubMed
31.
go back to reference True LD (1994) Surgical pathology examination of the prostate gland. Practice survey by American society of clinical pathologists. Am J Clin Pathol 102:572–579PubMed True LD (1994) Surgical pathology examination of the prostate gland. Practice survey by American society of clinical pathologists. Am J Clin Pathol 102:572–579PubMed
32.
go back to reference Upadhyay J, Shekarriz B, Nemeth JA, Dong Z, Cummings GD, Fridman R, Sakr W, Grignon DJ, Cher ML (1999) Membrane type 1-matrix metalloproteinase (MT1-MMP) and MMP-2 immunolocalization in human prostate: change in cellular localization associated with high-grade prostatic intraepithelial neoplasia. Clin Cancer Res 5:4105–4110PubMed Upadhyay J, Shekarriz B, Nemeth JA, Dong Z, Cummings GD, Fridman R, Sakr W, Grignon DJ, Cher ML (1999) Membrane type 1-matrix metalloproteinase (MT1-MMP) and MMP-2 immunolocalization in human prostate: change in cellular localization associated with high-grade prostatic intraepithelial neoplasia. Clin Cancer Res 5:4105–4110PubMed
33.
go back to reference Varani J, Hattori Y, Dame MK, Schmidt T, Murphy HS, Johnson KJ, Wojno KJ (2001) Matrix metalloproteinases (MMPs) in fresh human prostate tumour tissue and organ-cultured prostate tissue: levels of collagenolytic and gelatinolytic MMPs are low, variable and different in fresh tissue versus organ-cultured tissue. Br J Cancer 84:1076–1083CrossRefPubMed Varani J, Hattori Y, Dame MK, Schmidt T, Murphy HS, Johnson KJ, Wojno KJ (2001) Matrix metalloproteinases (MMPs) in fresh human prostate tumour tissue and organ-cultured prostate tissue: levels of collagenolytic and gelatinolytic MMPs are low, variable and different in fresh tissue versus organ-cultured tissue. Br J Cancer 84:1076–1083CrossRefPubMed
34.
go back to reference Woessner JF Jr (1991) Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J 5:2145–2154PubMed Woessner JF Jr (1991) Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J 5:2145–2154PubMed
35.
go back to reference Yamagata S, Yoshii Y, Suh JG, Tanaka R, Shimizu S (1991) Occurrence of an active form of gelatinase in human gastric and colorectal carcinoma tissues. Cancer Lett 59:51–55PubMed Yamagata S, Yoshii Y, Suh JG, Tanaka R, Shimizu S (1991) Occurrence of an active form of gelatinase in human gastric and colorectal carcinoma tissues. Cancer Lett 59:51–55PubMed
36.
go back to reference Zucker S, Hymowitz M, Conner C, Zarrabi HM, Hurewitz AN, Matrisian L, Boyd D, Nicolson G, Montana S (1999) Measurement of matrix metalloproteinases and tissue inhibitors of metalloproteinases in blood and tissues. Clinical and experimental applications. Ann N Y Acad Sci 878:212–227PubMed Zucker S, Hymowitz M, Conner C, Zarrabi HM, Hurewitz AN, Matrisian L, Boyd D, Nicolson G, Montana S (1999) Measurement of matrix metalloproteinases and tissue inhibitors of metalloproteinases in blood and tissues. Clinical and experimental applications. Ann N Y Acad Sci 878:212–227PubMed
Metadata
Title
Expression and activity of matrix metalloproteinases-2 and -9 in serum, core needle biopsies and tissue specimens of prostate cancer patients
Authors
Christian G. Sauer
Alexandra Kappeler
Monika Späth
Jens J. Kaden
Maurice S. Michel
Doris Mayer
Uwe Bleyl
Rainer Grobholz
Publication date
01-06-2004
Publisher
Springer-Verlag
Published in
Virchows Archiv / Issue 6/2004
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-004-1016-2

Other articles of this Issue 6/2004

Virchows Archiv 6/2004 Go to the issue

Announcements

June 2004