Skip to main content
Top
Published in: BMC Musculoskeletal Disorders 1/2018

Open Access 01-12-2018 | Research article

Expression of MMP-9 decreases metastatic potential of Chondrosarcoma: an immunohistochemical study

Authors: Dominik Malcherczyk, Thomas J. Heyse, Bilal F. El-Zayat, Vanessa Kunzke, Roland Moll, Susanne Fuchs-Winkelmann, Jürgen R. J. Paletta

Published in: BMC Musculoskeletal Disorders | Issue 1/2018

Login to get access

Abstract

Background

Chondrosarcoma is the second most common primary malignant bone tumor. Because of their heterogeneity, with differences in invasive and metastatic behavior, it is important to identify biological markers that will allow for a more accurate estimation of prognosis in patients with these tumors.
Matrix metalloproteinases (MMP) play a crucial role in tumor progression, invasion and metastasis. The mechanism of tumor progression dependent of MMPs is complex and influences malignant transformation, angiogenesis and tumor growth at the primary and metastatic sites. The purpose of this study was to investigate immunohistochemicaly the influence of MMP-1, MMP-3, MMP-9 and MMP-13 expression on prognostic parameter in chondrosarcoma.

Methods

We investigated tissue samples of 28 patients with chondrosarcoma. Immunohistochemical staining to evaluate the expression of MMP-1, MMP-3, MMP-9 and MMP-13 was performed. Subsequently, the expression level was correlated with metastatic potential, histological grading and overall survival in patients with this neoplasm.

Results

In consideration of semi quantitative scoring 64% of chondrosarcoma were scored as positive for MMP-1, 46% for MMP-3, 61% for MMP-9. The specimens had shown no expression of MMP-13. High expression of MMP-9 was associated with better histological differentiation, decreased metastatic potential and favourable overall survival. No correlation was found for expression of MMP-1, MMP-3 or MMP-13.

Conclusions

MMP-1, MMP-3 and MMP-9 are expressed in chondrosarcoma. Our findings suggest that the expression of MMP-9 is associated with clinical outcome parameters in chondrosarcoma.
Literature
2.
go back to reference Damron TA, Ward WG, Stewart A. Osteosarcoma, chondrosarcoma, and Ewing's sarcoma: national cancer data base report. Clin Orthop Relat Res. 2007;459:40–7.CrossRefPubMed Damron TA, Ward WG, Stewart A. Osteosarcoma, chondrosarcoma, and Ewing's sarcoma: national cancer data base report. Clin Orthop Relat Res. 2007;459:40–7.CrossRefPubMed
3.
go back to reference Lee FY, Mankin HJ, Fondren G, Gebhardt MC, Springfield DS, Rosenberg AE, et al. Chondrosarcoma of bone: an assessment of outcome. J Bone Joint Surg Am. 1999;81(3):326–38.CrossRefPubMed Lee FY, Mankin HJ, Fondren G, Gebhardt MC, Springfield DS, Rosenberg AE, et al. Chondrosarcoma of bone: an assessment of outcome. J Bone Joint Surg Am. 1999;81(3):326–38.CrossRefPubMed
4.
go back to reference Ogura K, Fujiwara T, Beppu Y, Chuman H, Yoshida A, Kawano H, et al. Extraskeletal myxoid chondrosarcoma: a review of 23 patients treated at a single referral center with long-term follow-up. Arch Orthop Trauma Surg. 2012;132(10):1379–86.CrossRefPubMed Ogura K, Fujiwara T, Beppu Y, Chuman H, Yoshida A, Kawano H, et al. Extraskeletal myxoid chondrosarcoma: a review of 23 patients treated at a single referral center with long-term follow-up. Arch Orthop Trauma Surg. 2012;132(10):1379–86.CrossRefPubMed
5.
go back to reference Heyse TJ, Malcherczyk D, Moll R, Timmesfeld N, Wapelhorst J, Fuchs-Winkelmann S, et al. CD44: survival and metastasis in chondrosarcoma. Osteoarthr Cartil. 2010;18(6):849–56.CrossRefPubMed Heyse TJ, Malcherczyk D, Moll R, Timmesfeld N, Wapelhorst J, Fuchs-Winkelmann S, et al. CD44: survival and metastasis in chondrosarcoma. Osteoarthr Cartil. 2010;18(6):849–56.CrossRefPubMed
6.
go back to reference Papachristou DJ, Gkretsi V, Rao UN, Papachristou GI, Papaefthymiou OA, Basdra EK, et al. Expression of integrin-linked kinase and its binding partners in chondrosarcoma: association with prognostic significance. Eur J Cancer. 2008;44(16):2518–25.CrossRefPubMedPubMedCentral Papachristou DJ, Gkretsi V, Rao UN, Papachristou GI, Papaefthymiou OA, Basdra EK, et al. Expression of integrin-linked kinase and its binding partners in chondrosarcoma: association with prognostic significance. Eur J Cancer. 2008;44(16):2518–25.CrossRefPubMedPubMedCentral
7.
go back to reference Takeuchi A, Yamamoto Y, Tsuneyama K, Cheng C, Yonekura H, Watanabe T, et al. Endogenous secretory receptor for advanced glycation endproducts as a novel prognostic marker in chondrosarcoma. Cancer. 2007;109(12):2532–40.CrossRefPubMed Takeuchi A, Yamamoto Y, Tsuneyama K, Cheng C, Yonekura H, Watanabe T, et al. Endogenous secretory receptor for advanced glycation endproducts as a novel prognostic marker in chondrosarcoma. Cancer. 2007;109(12):2532–40.CrossRefPubMed
8.
go back to reference Yoshimura Y, Isobe K, Arai H, Aoki K, Kito M, Kato H. Preoperative radiographic and histopathologic evaluation of central chondrosarcoma. Arch Orthop Trauma Surg. 2013;133(9):1225–31.CrossRefPubMedPubMedCentral Yoshimura Y, Isobe K, Arai H, Aoki K, Kito M, Kato H. Preoperative radiographic and histopathologic evaluation of central chondrosarcoma. Arch Orthop Trauma Surg. 2013;133(9):1225–31.CrossRefPubMedPubMedCentral
9.
go back to reference Friedl P, Wolf K. Tube travel: the role of proteases in individual and collective cancer cell invasion. Cancer Res. 2008;68(18):7247–9.CrossRefPubMed Friedl P, Wolf K. Tube travel: the role of proteases in individual and collective cancer cell invasion. Cancer Res. 2008;68(18):7247–9.CrossRefPubMed
10.
go back to reference Klein T, Bischoff R. Physiology and pathophysiology of matrix metalloproteases. Amino Acids. 2011;41(2):271–90.CrossRefPubMed Klein T, Bischoff R. Physiology and pathophysiology of matrix metalloproteases. Amino Acids. 2011;41(2):271–90.CrossRefPubMed
11.
go back to reference Martin MD, Matrisian LM. The other side of MMPs: protective roles in tumor progression. Cancer Metastasis Rev. 2007;26(3–4):717–24.CrossRefPubMed Martin MD, Matrisian LM. The other side of MMPs: protective roles in tumor progression. Cancer Metastasis Rev. 2007;26(3–4):717–24.CrossRefPubMed
12.
go back to reference Hua H, Li M, Luo T, Yin Y, Jiang Y. Matrix metalloproteinases in tumorigenesis: an evolving paradigm. Cell Mol Life Sci. 2011;68(23):3853–68.CrossRefPubMed Hua H, Li M, Luo T, Yin Y, Jiang Y. Matrix metalloproteinases in tumorigenesis: an evolving paradigm. Cell Mol Life Sci. 2011;68(23):3853–68.CrossRefPubMed
13.
go back to reference García MF, González-Reyes S, González LO, Junquera S, Berdize N, Del Casar JM, et al. Comparative study of the expression of metalloproteases and their inhibitors in different localizations within primary tumours and in metastatic lymph nodes of breast cancer. Int J Exp Pathol. 2010;91(4):324–34.CrossRefPubMedPubMedCentral García MF, González-Reyes S, González LO, Junquera S, Berdize N, Del Casar JM, et al. Comparative study of the expression of metalloproteases and their inhibitors in different localizations within primary tumours and in metastatic lymph nodes of breast cancer. Int J Exp Pathol. 2010;91(4):324–34.CrossRefPubMedPubMedCentral
14.
go back to reference Dreier R, Grässel S, Fuchs S, Schaumburger J, Bruckner P. Pro-MMP-9 is a specific macrophage product and is activated by osteoarthritic chondrocytes via MMP-3 or a MT1-MMP/MMP-13 cascade. Exp Cell Res. 2004;297(2):303–12.CrossRefPubMed Dreier R, Grässel S, Fuchs S, Schaumburger J, Bruckner P. Pro-MMP-9 is a specific macrophage product and is activated by osteoarthritic chondrocytes via MMP-3 or a MT1-MMP/MMP-13 cascade. Exp Cell Res. 2004;297(2):303–12.CrossRefPubMed
15.
go back to reference Deryugina EI, Quigley JP. Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev. 2006;25(1):9–34.CrossRefPubMed Deryugina EI, Quigley JP. Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev. 2006;25(1):9–34.CrossRefPubMed
16.
go back to reference Michael M, Babic B, Khokha R, Tsao M, Ho J, Pintilie M, et al. Expression and prognostic significance of metalloproteinases and their tissue inhibitors in patients with small-cell lung cancer. J Clin Oncol. 1999;17(6):1802–8.CrossRefPubMed Michael M, Babic B, Khokha R, Tsao M, Ho J, Pintilie M, et al. Expression and prognostic significance of metalloproteinases and their tissue inhibitors in patients with small-cell lung cancer. J Clin Oncol. 1999;17(6):1802–8.CrossRefPubMed
17.
go back to reference Talvensaari-Mattila A, Pääkkö P, Turpeenniemi-Hujanen T. Matrix metalloproteinase-2 (MMP-2) is associated with survival in breast carcinoma. Br J Cancer. 2003;89(7):1270–5.CrossRefPubMedPubMedCentral Talvensaari-Mattila A, Pääkkö P, Turpeenniemi-Hujanen T. Matrix metalloproteinase-2 (MMP-2) is associated with survival in breast carcinoma. Br J Cancer. 2003;89(7):1270–5.CrossRefPubMedPubMedCentral
18.
go back to reference Bando E, Yonemura Y, Endou Y, Sasaki T, Taniguchi K, Fujita H, et al. Immunohistochemical study of MT-MMP tissue status in gastric carcinoma and correlation with survival analyzed by univariate and multivariate analysis. Oncol Rep. 1998;5(6):1483–8.PubMed Bando E, Yonemura Y, Endou Y, Sasaki T, Taniguchi K, Fujita H, et al. Immunohistochemical study of MT-MMP tissue status in gastric carcinoma and correlation with survival analyzed by univariate and multivariate analysis. Oncol Rep. 1998;5(6):1483–8.PubMed
19.
go back to reference Agarwal D, Goodison S, Nicholson B, Tarin D, Urquidi V. Expression of matrix metalloproteinase 8 (MMP-8) and tyrosinase-related protein-1 (TYRP-1) correlates with the absence of metastasis in an isogenic human breast cancer model. Differentiation. 2003;71(2):114–25.CrossRefPubMed Agarwal D, Goodison S, Nicholson B, Tarin D, Urquidi V. Expression of matrix metalloproteinase 8 (MMP-8) and tyrosinase-related protein-1 (TYRP-1) correlates with the absence of metastasis in an isogenic human breast cancer model. Differentiation. 2003;71(2):114–25.CrossRefPubMed
20.
go back to reference McCawley LJ, Crawford HC, King LE, Mudgett J, Matrisian LMA. Protective role for matrix metalloproteinase-3 in squamous cell carcinoma. Cancer Res. 2004;64(19):6965–72.CrossRefPubMed McCawley LJ, Crawford HC, King LE, Mudgett J, Matrisian LMA. Protective role for matrix metalloproteinase-3 in squamous cell carcinoma. Cancer Res. 2004;64(19):6965–72.CrossRefPubMed
21.
go back to reference Noël A, Gutiérrez-Fernández A, Sounni NE, Behrendt N, Maquoi E, Lund IK, et al. New and paradoxical roles of matrix metalloproteinases in the tumor microenvironment. Front Pharmacol. 2012;3:140.PubMedPubMedCentral Noël A, Gutiérrez-Fernández A, Sounni NE, Behrendt N, Maquoi E, Lund IK, et al. New and paradoxical roles of matrix metalloproteinases in the tumor microenvironment. Front Pharmacol. 2012;3:140.PubMedPubMedCentral
22.
go back to reference Uchibori M, Nishida Y, Nagasaka T, Yamada Y, Nakanishi K, Ishiguro N. Increased expression of membrane-type matrix metalloproteinase-1 is correlated with poor prognosis in patients with osteosarcoma. Int J Oncol. 2006;28(1):33–42.PubMed Uchibori M, Nishida Y, Nagasaka T, Yamada Y, Nakanishi K, Ishiguro N. Increased expression of membrane-type matrix metalloproteinase-1 is correlated with poor prognosis in patients with osteosarcoma. Int J Oncol. 2006;28(1):33–42.PubMed
23.
go back to reference Sugita H, Osaka S, Toriyama M, Osaka E, Yoshida Y, Ryu J, et al. Correlation between the histological grade of chondrosarcoma and the expression of MMPs, ADAMTSs and TIMPs. Anticancer Res. 2004;24(6):4079–84.PubMed Sugita H, Osaka S, Toriyama M, Osaka E, Yoshida Y, Ryu J, et al. Correlation between the histological grade of chondrosarcoma and the expression of MMPs, ADAMTSs and TIMPs. Anticancer Res. 2004;24(6):4079–84.PubMed
24.
go back to reference Luukkaa H, Klemi P, Leivo I, Mäkitie AA, Irish J, Gilbert R, et al. Expression of matrix metalloproteinase-1, −7, −9, −13, Ki-67, and HER-2 in epithelial-myoepithelial salivary gland cancer. Head Neck. 2010;32(8):1019–27.CrossRefPubMed Luukkaa H, Klemi P, Leivo I, Mäkitie AA, Irish J, Gilbert R, et al. Expression of matrix metalloproteinase-1, −7, −9, −13, Ki-67, and HER-2 in epithelial-myoepithelial salivary gland cancer. Head Neck. 2010;32(8):1019–27.CrossRefPubMed
25.
go back to reference Voland P, Besig S, Rad R, Braun T, Baur DM, Perren A, et al. Correlation of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinase expression in ileal carcinoids, lymph nodes and liver metastasis with prognosis and survival. Neuroendocrinology. 2009;89(1):66–78.CrossRefPubMed Voland P, Besig S, Rad R, Braun T, Baur DM, Perren A, et al. Correlation of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinase expression in ileal carcinoids, lymph nodes and liver metastasis with prognosis and survival. Neuroendocrinology. 2009;89(1):66–78.CrossRefPubMed
26.
go back to reference Aresu L, Giantin M, Morello E, Vascellari M, Castagnaro M, Lopparelli R, et al. Matrix metalloproteinases and their inhibitors in canine mammary tumors. BMC Vet Res. 2011;7:33.CrossRefPubMedPubMedCentral Aresu L, Giantin M, Morello E, Vascellari M, Castagnaro M, Lopparelli R, et al. Matrix metalloproteinases and their inhibitors in canine mammary tumors. BMC Vet Res. 2011;7:33.CrossRefPubMedPubMedCentral
27.
go back to reference Benassi MS, Gamberi G, Magagnoli G, Molendini L, Ragazzini P, Merli M, et al. Metalloproteinase expression and prognosis in soft tissue sarcomas. Ann Oncol. 2001;12(1):75–80.CrossRefPubMed Benassi MS, Gamberi G, Magagnoli G, Molendini L, Ragazzini P, Merli M, et al. Metalloproteinase expression and prognosis in soft tissue sarcomas. Ann Oncol. 2001;12(1):75–80.CrossRefPubMed
28.
go back to reference Korpi JT, Hagström J, Lehtonen N, Parkkinen J, Sorsa T, Salo T, et al. Expression of matrix metalloproteinases-2, −8, −13, −26, and tissue inhibitors of metalloproteinase-1 in human osteosarcoma. Surg Oncol. 2011;20(1):e18–22.CrossRefPubMed Korpi JT, Hagström J, Lehtonen N, Parkkinen J, Sorsa T, Salo T, et al. Expression of matrix metalloproteinases-2, −8, −13, −26, and tissue inhibitors of metalloproteinase-1 in human osteosarcoma. Surg Oncol. 2011;20(1):e18–22.CrossRefPubMed
29.
go back to reference Söderström M, Aro HT, Ahonen M, Johansson N, Aho A, Ekfors T, et al. Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human chondrosarcomas. APMIS. 2001;109(4):305–15.CrossRefPubMed Söderström M, Aro HT, Ahonen M, Johansson N, Aho A, Ekfors T, et al. Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human chondrosarcomas. APMIS. 2001;109(4):305–15.CrossRefPubMed
30.
go back to reference Sakamoto A, Oda Y, Iwamoto Y, Tsuneyoshi M. Expression of membrane type 1 matrix metalloproteinase, matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 in human cartilaginous tumors with special emphasis on mesenchymal and dedifferentiated chondrosarcoma. J Cancer Res Clin Oncol. 1999;125(10):541–8.CrossRefPubMed Sakamoto A, Oda Y, Iwamoto Y, Tsuneyoshi M. Expression of membrane type 1 matrix metalloproteinase, matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 in human cartilaginous tumors with special emphasis on mesenchymal and dedifferentiated chondrosarcoma. J Cancer Res Clin Oncol. 1999;125(10):541–8.CrossRefPubMed
31.
go back to reference Scully SP, Berend KR, Qi WN, Harrelson JM. Collagenase specificity in chondrosarcoma metastasis. Braz J Med Biol Res. 1999;32(7):885–9.CrossRefPubMed Scully SP, Berend KR, Qi WN, Harrelson JM. Collagenase specificity in chondrosarcoma metastasis. Braz J Med Biol Res. 1999;32(7):885–9.CrossRefPubMed
32.
go back to reference Takahashi M, Oka N, Naroda T, Nishitani MA, Kanda K, Kanayama HO, et al. Prognostic significance of matrix metalloproteinases-2 activation ratio in renal cell carcinoma. Int J Urol. 2002;9(10):531–8.CrossRefPubMed Takahashi M, Oka N, Naroda T, Nishitani MA, Kanda K, Kanayama HO, et al. Prognostic significance of matrix metalloproteinases-2 activation ratio in renal cell carcinoma. Int J Urol. 2002;9(10):531–8.CrossRefPubMed
33.
go back to reference Svagzdys S, Lesauskaite V, Pangonyte D, Saladzinskas Z, Tamelis A, Pavalkis D. Matrix metalloproteinase-9 is a prognostic marker to predict survival of patients who underwent surgery due to rectal carcinoma. Tohoku J Exp Med. 2011;223(1):67–73.CrossRefPubMed Svagzdys S, Lesauskaite V, Pangonyte D, Saladzinskas Z, Tamelis A, Pavalkis D. Matrix metalloproteinase-9 is a prognostic marker to predict survival of patients who underwent surgery due to rectal carcinoma. Tohoku J Exp Med. 2011;223(1):67–73.CrossRefPubMed
34.
go back to reference Pozzi A, Moberg PE, Miles LA, Wagner S, Soloway P, Gardner HA. Elevated matrix metalloprotease and angiostatin levels in integrin alpha 1 knockout mice cause reduced tumor vascularization. Proc Natl Acad Sci U S A. 2000;97(5):2202–7.CrossRefPubMedPubMedCentral Pozzi A, Moberg PE, Miles LA, Wagner S, Soloway P, Gardner HA. Elevated matrix metalloprotease and angiostatin levels in integrin alpha 1 knockout mice cause reduced tumor vascularization. Proc Natl Acad Sci U S A. 2000;97(5):2202–7.CrossRefPubMedPubMedCentral
35.
go back to reference Bendrik C, Robertson J, Gauldie J, Dabrosin C. Gene transfer of matrix metalloproteinase-9 induces tumor regression of breast cancer in vivo. Cancer Res. 2008;68(9):3405–12.CrossRefPubMed Bendrik C, Robertson J, Gauldie J, Dabrosin C. Gene transfer of matrix metalloproteinase-9 induces tumor regression of breast cancer in vivo. Cancer Res. 2008;68(9):3405–12.CrossRefPubMed
36.
go back to reference Furumatsu T, Yamaguchi N, Nishida K, Kawai A, Kunisada T, Namba M, et al. Endostatin inhibits adhesion of endothelial cells to collagen I via alpha(2)beta(1) integrin, a possible cause of prevention of chondrosarcoma growth. J Biochem. 2002;131(4):619–26.CrossRefPubMed Furumatsu T, Yamaguchi N, Nishida K, Kawai A, Kunisada T, Namba M, et al. Endostatin inhibits adhesion of endothelial cells to collagen I via alpha(2)beta(1) integrin, a possible cause of prevention of chondrosarcoma growth. J Biochem. 2002;131(4):619–26.CrossRefPubMed
37.
go back to reference Hamano Y, Zeisberg M, Sugimoto H, Lively JC, Maeshima Y, Yang C, et al. Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphaV beta3 integrin. Cancer Cell. 2003;3(6):589–601.CrossRefPubMedPubMedCentral Hamano Y, Zeisberg M, Sugimoto H, Lively JC, Maeshima Y, Yang C, et al. Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphaV beta3 integrin. Cancer Cell. 2003;3(6):589–601.CrossRefPubMedPubMedCentral
Metadata
Title
Expression of MMP-9 decreases metastatic potential of Chondrosarcoma: an immunohistochemical study
Authors
Dominik Malcherczyk
Thomas J. Heyse
Bilal F. El-Zayat
Vanessa Kunzke
Roland Moll
Susanne Fuchs-Winkelmann
Jürgen R. J. Paletta
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2018
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-017-1920-7

Other articles of this Issue 1/2018

BMC Musculoskeletal Disorders 1/2018 Go to the issue