Skip to main content
Erschienen in: Endocrine 1/2017

22.03.2017 | Original Article

Matrix metalloproteinase 2 (MMP-2) levels are increased in active acromegaly patients

verfasst von: Alper Cagri Karci, Zeynep Canturk, Ilhan Tarkun, Berrin Cetinarslan

Erschienen in: Endocrine | Ausgabe 1/2017

Einloggen, um Zugang zu erhalten

Abstract

Purpose

During follow-up of acromegaly patients, there is a discordance rate of 30% between the measurements of growth hormone and insulin-like growth factor-1 levels. Further tests are required to determine disease activity in patients with discordant results. This study was planned to investigate an association of serum levels of matrix metalloproteinase-2, matrix metalloproteinase-9, and cathepsin B with disease activity in acromegaly patients.

Methods

In this study, 64 acromegaly patients followed in our clinic were divided into two groups according to the 2010 consensus criteria for cure of acromegaly as patients with active disease (n = 24) and patients with controlled disease (n = 40). Serum matrix metalloproteinase-2, matrix metalloproteinase-9, and cathepsin B levels were measured by the enzyme-linked immunosorbent assay method.

Results

The mean serum matrix metalloproteinase-2 level was significantly higher in the active acromegaly patients than in the controlled acromegaly patients (150.1 ± 54.5 ng/mL vs. 100.2 ± 44.6 ng/mL; p < 0.0001). There was no significant difference between the active and controlled acromegaly patients regarding serum matrix metalloproteinase-9 and cathepsin B levels (p = 0.205 and p = 0.598, respectively). Serum matrix metalloproteinase-2 levels of 118.3 ng/mL and higher had a sensitivity of 75% and a specificity of 77.5% in determining active disease. The risk of active acromegaly was 3.3 fold higher in the patients with a matrix metalloproteinase-2 level of >118.3 ng/mL than in the patients with a matrix metalloproteinase-2 level of <118.3 ng/mL.

Conclusions

In this study, serum matrix metalloproteinase-2 level is increased in the active acromegaly patients and a threshold value in determining active disease was defined for serum matrix metalloproteinase-2 level. This study is the first to compare acromegaly patients having active or controlled disease in terms of matrix metalloproteinase-2 and matrix metalloproteinase-9 levels. The results need to be confirmed by a study that will be conducted in a larger patient group also including a healthy control group to demonstrate the value of this novel marker in disease activity.
Literatur
1.
Zurück zum Zitat S. Melmed, Medical progress: acromegaly. N. Eng. J. Med. 355, 2558–2573 (2006)CrossRef S. Melmed, Medical progress: acromegaly. N. Eng. J. Med. 355, 2558–2573 (2006)CrossRef
2.
Zurück zum Zitat S. Melmed, A. Colao, A. Barkan, M. Molitch, A.B. Grossman, D. Klienberg, D. Clemmons, P. Chanson, E. Laws, J. Schlechte, M.L. Vance, K. Ho, A. Giustina; Acromegaly Consensus Group., guidelines for acromegaly management: an update. J. Clin. Endocrinol. Metab. 94, 1509–1517 (2009)CrossRef S. Melmed, A. Colao, A. Barkan, M. Molitch, A.B. Grossman, D. Klienberg, D. Clemmons, P. Chanson, E. Laws, J. Schlechte, M.L. Vance, K. Ho, A. Giustina; Acromegaly Consensus Group., guidelines for acromegaly management: an update. J. Clin. Endocrinol. Metab. 94, 1509–1517 (2009)CrossRef
3.
Zurück zum Zitat E.O. Machado, G.F. Taboada, L.V. Neto, F.R. van Haute, L.L. Corrêa, G.A. Balarini, Y. Shrank, M. Goulart, M.R. Gadelha, Prevalence of discordant GH and IGF-I levels in acromegalics at diagnosis, after surgical treatment and during treatment with octreotide LAR. Growth. Horm. IGF Res. 18, 389–393 (2008)CrossRef E.O. Machado, G.F. Taboada, L.V. Neto, F.R. van Haute, L.L. Corrêa, G.A. Balarini, Y. Shrank, M. Goulart, M.R. Gadelha, Prevalence of discordant GH and IGF-I levels in acromegalics at diagnosis, after surgical treatment and during treatment with octreotide LAR. Growth. Horm. IGF Res. 18, 389–393 (2008)CrossRef
4.
Zurück zum Zitat I.M. Holdaway, M.J. Bolland, G.D. Gamble, A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly. Eur. J. Endocrinol 159, 89–95 (2008)CrossRef I.M. Holdaway, M.J. Bolland, G.D. Gamble, A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly. Eur. J. Endocrinol 159, 89–95 (2008)CrossRef
5.
Zurück zum Zitat M.R. Farnoud, F. Farhadian, J.L. Samuel, P. Derome, F. Peillon, J.Y. Li, Fibronectin isoforms are differentially expressed in normal and adenomatous human anterior pituitaries. Int. J. Cancer 61, 27–34 (1995)CrossRef M.R. Farnoud, F. Farhadian, J.L. Samuel, P. Derome, F. Peillon, J.Y. Li, Fibronectin isoforms are differentially expressed in normal and adenomatous human anterior pituitaries. Int. J. Cancer 61, 27–34 (1995)CrossRef
6.
Zurück zum Zitat K. Thapar, K. Kovacs, B.W. Scheithauer, L. Stefaneanu, E. Horvath, P.J. Pernicone, D. Murray, E.R. Laws Jr., Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody. Neurosurgery 38, 99–106 (1996)CrossRef K. Thapar, K. Kovacs, B.W. Scheithauer, L. Stefaneanu, E. Horvath, P.J. Pernicone, D. Murray, E.R. Laws Jr., Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody. Neurosurgery 38, 99–106 (1996)CrossRef
7.
Zurück zum Zitat A. Page-McCaw, A.J. Ewald, Z. Werb, Matrix metalloproteinases and the regulation of tissue remodelling. Nat. Rev. Mol. Cell Biol. 8, 221–233 (2007)CrossRef A. Page-McCaw, A.J. Ewald, Z. Werb, Matrix metalloproteinases and the regulation of tissue remodelling. Nat. Rev. Mol. Cell Biol. 8, 221–233 (2007)CrossRef
8.
Zurück zum Zitat A. Nagase, R. Visse, G. Murphy, Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc. Res. 69, 562–573 (2006)CrossRef A. Nagase, R. Visse, G. Murphy, Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc. Res. 69, 562–573 (2006)CrossRef
9.
Zurück zum Zitat M.J. Duff, The role of proteolytic enzymes in cancer invasion and metastasis. Clin. Exp. Metastasis. 10, 145–155 (1992)CrossRef M.J. Duff, The role of proteolytic enzymes in cancer invasion and metastasis. Clin. Exp. Metastasis. 10, 145–155 (1992)CrossRef
10.
Zurück zum Zitat H. Kawamoto, T. Uozomi, K. Kawamoto, K. Arita, Y. Yano, T. Hirohata, Type IV collagenase activity and cavernous sinus invasion in human pituitary adenomas. Acta Neurochir. (Wien). 138, 390–395 (1996)CrossRef H. Kawamoto, T. Uozomi, K. Kawamoto, K. Arita, Y. Yano, T. Hirohata, Type IV collagenase activity and cavernous sinus invasion in human pituitary adenomas. Acta Neurochir. (Wien). 138, 390–395 (1996)CrossRef
11.
Zurück zum Zitat W. Liu, Y. Matsumoto, M. Okada, K. Miyake, K. Kunishio, N. Kawai, T. Tamiya, S. Nagao, Matrix metalloproteinase 2 and 9 expression correlated with cavernous sinus invasion of pituitary adenomas. J. Med. Invest. 52, 151–158 (2005)CrossRef W. Liu, Y. Matsumoto, M. Okada, K. Miyake, K. Kunishio, N. Kawai, T. Tamiya, S. Nagao, Matrix metalloproteinase 2 and 9 expression correlated with cavernous sinus invasion of pituitary adenomas. J. Med. Invest. 52, 151–158 (2005)CrossRef
12.
Zurück zum Zitat E. Beaulieu, Z. Kachra, N. Mousseau, L. Delbecchi, J. Hardy, R. Béliveau, Matrix metalloproteinases and their inhibitors in human pituitary tumors. Neurosurgery 45, 1432–1440 (1999)CrossRef E. Beaulieu, Z. Kachra, N. Mousseau, L. Delbecchi, J. Hardy, R. Béliveau, Matrix metalloproteinases and their inhibitors in human pituitary tumors. Neurosurgery 45, 1432–1440 (1999)CrossRef
13.
Zurück zum Zitat S. Yokoyama, H. Hirano, K. Moraki, M. Goto, S. Imamura, J.I. Kuratsu, Are nonfunctioning pituitary adenomas extending into the cavernous sinus aggressive and/or invasive? Neurosurgery 49, 857–862 (2001)PubMed S. Yokoyama, H. Hirano, K. Moraki, M. Goto, S. Imamura, J.I. Kuratsu, Are nonfunctioning pituitary adenomas extending into the cavernous sinus aggressive and/or invasive? Neurosurgery 49, 857–862 (2001)PubMed
14.
Zurück zum Zitat U.J. Knappe, C. Hagel, B.W. Lisboa, W. Wilczak, D.K. Lüdecke, W. Saeger, Expression of serine proteases and metalloproteinases in human pituitary adenomas and anterior pituitary lobe tissue. Acta Neuropathol. 106, 471–478 (2003)CrossRef U.J. Knappe, C. Hagel, B.W. Lisboa, W. Wilczak, D.K. Lüdecke, W. Saeger, Expression of serine proteases and metalloproteinases in human pituitary adenomas and anterior pituitary lobe tissue. Acta Neuropathol. 106, 471–478 (2003)CrossRef
15.
Zurück zum Zitat M. Páez Pereda, M.F. Ledda, V. Goldberg, A. Chervín, G. Carrizo, H. Molina, A. Müller, U. Renner, O. Podhajcer, E. Arzt, G.K. Stalla, High levels of matrix metalloproteinases regulate proliferation and hormone secretion in pituitary cells. J. Clin. Endocrinol. Metab. 85, 263–269 (2000)PubMed M. Páez Pereda, M.F. Ledda, V. Goldberg, A. Chervín, G. Carrizo, H. Molina, A. Müller, U. Renner, O. Podhajcer, E. Arzt, G.K. Stalla, High levels of matrix metalloproteinases regulate proliferation and hormone secretion in pituitary cells. J. Clin. Endocrinol. Metab. 85, 263–269 (2000)PubMed
16.
Zurück zum Zitat J. Daroszewski, M. Bolanowski, M. Kaluzny, M. Siewinski, The imbalance of cathepsin B-like activity in acromegalic patients-preliminary report. Neuro. Endocrinol. Lett. 31, 256–260 (2010)PubMed J. Daroszewski, M. Bolanowski, M. Kaluzny, M. Siewinski, The imbalance of cathepsin B-like activity in acromegalic patients-preliminary report. Neuro. Endocrinol. Lett. 31, 256–260 (2010)PubMed
17.
Zurück zum Zitat A. Giustina, P. Chanson, M.D. Bronstein, A. Klibanski, S. Lamberts, F.F. Casanueva, P. Trainer, E. Ghigo, K. Ho, S. Melmed; Acromegaly Consensus Group., A consensus on criteria for cure of acromegaly. J. Clin. Endocrinol. Metab. 95, 3141–3148 (2010)CrossRef A. Giustina, P. Chanson, M.D. Bronstein, A. Klibanski, S. Lamberts, F.F. Casanueva, P. Trainer, E. Ghigo, K. Ho, S. Melmed; Acromegaly Consensus Group., A consensus on criteria for cure of acromegaly. J. Clin. Endocrinol. Metab. 95, 3141–3148 (2010)CrossRef
18.
Zurück zum Zitat K. Yoshimura, T. Tsuchida, K. Kawamoto, Expression of cathepsin B and cystatin C in the human adenohypophysis and in pituitary adenomas. Oncol. Rep. 7, 27–31 (2000)PubMed K. Yoshimura, T. Tsuchida, K. Kawamoto, Expression of cathepsin B and cystatin C in the human adenohypophysis and in pituitary adenomas. Oncol. Rep. 7, 27–31 (2000)PubMed
19.
Zurück zum Zitat I. Berdowska, Cysteine proteases as disease markers. Clin. Chim. Acta 342, 41–69 (2004)CrossRef I. Berdowska, Cysteine proteases as disease markers. Clin. Chim. Acta 342, 41–69 (2004)CrossRef
20.
Zurück zum Zitat A.N. Paisley, C.J. O’Callaghan, K.C. Lewandowski, C. Parkinson, M.E. Roberts, W.M. Drake, J.P. Monson, P.J. Trainer, H.S. Randeva, Reductions of circulating matrix metalloproteinase 2 and vascular endothelial growth factor levels after treatment with pegvisomant in subjects with acromegaly. J. Clin. Endocrinol. Metab. 91, 4635–4640 (2006)CrossRef A.N. Paisley, C.J. O’Callaghan, K.C. Lewandowski, C. Parkinson, M.E. Roberts, W.M. Drake, J.P. Monson, P.J. Trainer, H.S. Randeva, Reductions of circulating matrix metalloproteinase 2 and vascular endothelial growth factor levels after treatment with pegvisomant in subjects with acromegaly. J. Clin. Endocrinol. Metab. 91, 4635–4640 (2006)CrossRef
21.
Zurück zum Zitat G.A. Kanakis, A. Chrisoulidou, A. Bargiota, L. Efstathiadou, A. Papanastasiou, A. Theodoropoulou, S.K. Tigas, D.A. Vassiliadi, S. Tsagarakis, M. Alevizaki, The ongoing challenge of discrepant growth hormone and insulin-like growth factor I results in the evaluation of treated acromegalic patients: a systematic review and meta analysis. Clin. Endocrinol. (Oxf). 85, 681–688 (2016)CrossRef G.A. Kanakis, A. Chrisoulidou, A. Bargiota, L. Efstathiadou, A. Papanastasiou, A. Theodoropoulou, S.K. Tigas, D.A. Vassiliadi, S. Tsagarakis, M. Alevizaki, The ongoing challenge of discrepant growth hormone and insulin-like growth factor I results in the evaluation of treated acromegalic patients: a systematic review and meta analysis. Clin. Endocrinol. (Oxf). 85, 681–688 (2016)CrossRef
22.
Zurück zum Zitat E.T. Cerit, K. Ağbaht, Ö. Demir, M. Şahin, V.T. Gedik, C. Özcan, D. Çorapçıoğlu, Discordance between GH and IGF-1 levels in Turkish acromegalic patients. Endocr. Pract. 22, 1422–1428 (2016)CrossRef E.T. Cerit, K. Ağbaht, Ö. Demir, M. Şahin, V.T. Gedik, C. Özcan, D. Çorapçıoğlu, Discordance between GH and IGF-1 levels in Turkish acromegalic patients. Endocr. Pract. 22, 1422–1428 (2016)CrossRef
23.
Zurück zum Zitat P.U. Freda, Monitoring of acromegaly: what should be performed when GH and IGF-1 levels are discrepant? Clin. Endocrinol. (Oxf). 71, 166–170 (2009)CrossRef P.U. Freda, Monitoring of acromegaly: what should be performed when GH and IGF-1 levels are discrepant? Clin. Endocrinol. (Oxf). 71, 166–170 (2009)CrossRef
24.
Zurück zum Zitat H.J. Kim, S.H. Kwon, S.W. Kim, D.J. Park, C.S. Shin, K.S. Park, S.Y. Kim, B.Y. Cho, H.K. Lee, Diagnostic value of serum IGF-I and IGFBP-3 in growth hormone disorders in adults. Horm. Res. 56, 117–123 (2001)PubMed H.J. Kim, S.H. Kwon, S.W. Kim, D.J. Park, C.S. Shin, K.S. Park, S.Y. Kim, B.Y. Cho, H.K. Lee, Diagnostic value of serum IGF-I and IGFBP-3 in growth hormone disorders in adults. Horm. Res. 56, 117–123 (2001)PubMed
25.
Zurück zum Zitat M. Arosio, S. Garrone, P. Bruzzi, G. Faglia, F. Minuto, A. Barreca, Diagnostic value of the acid-labile subunit in acromegaly: evaluation in comparison with insulin-like growth factor (IGF) I, and IGF-binding protein 1, -2, -3. J. Clin. Endocrinol. Metab. 86, 1091–1098 (2001)PubMed M. Arosio, S. Garrone, P. Bruzzi, G. Faglia, F. Minuto, A. Barreca, Diagnostic value of the acid-labile subunit in acromegaly: evaluation in comparison with insulin-like growth factor (IGF) I, and IGF-binding protein 1, -2, -3. J. Clin. Endocrinol. Metab. 86, 1091–1098 (2001)PubMed
Metadaten
Titel
Matrix metalloproteinase 2 (MMP-2) levels are increased in active acromegaly patients
verfasst von
Alper Cagri Karci
Zeynep Canturk
Ilhan Tarkun
Berrin Cetinarslan
Publikationsdatum
22.03.2017
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 1/2017
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-017-1283-8

Weitere Artikel der Ausgabe 1/2017

Endocrine 1/2017 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.