Relationship between matrix metalloproteinases and the occurrence and development of ovarian cancer

Zhang, Y.; Chen, Q.

doi:10.1590/1414-431X20176104

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Brazilian Journal of Medical and Biological Research

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Reviews • Braz. J. Med. Biol. Res. 50 (6) • 2017 • https://doi.org/10.1590/1414-431X20176104 copy

Relationship between matrix metalloproteinases and the occurrence and development of ovarian cancer

Authorship SCIMAGO INSTITUTIONS RANKINGS

Ovarian cancer is one of the most malignant genital cancers, with a high mortality rate. Many researchers have suggested that matrix metalloproteinases (MMPs) have remarkably high expression in ovarian cancer tissues. MMPs are considered to be related to the occurrence, development, invasion and metastasis of ovarian cancer. Moreover, some studies have discovered that the unbalance between MMPs and tissue inhibitor of metalloproteinases (TIMPs) are associated with the malignant phenotype of tumors. This review summarizes the latest research progress of MMPs in ovarian cancer. The investigation of MMP mechanism in ovarian cancer will facilitate the development of effective anti-tumor drugs, and thereby improve the survival rate of patients with ovarian cancer.

Ovarian cancer; Matrix metalloproteinases (MMPs); Tissue inhibitor of metalloproteinases (TIMPs); Invasion; Metastasis

Author, year	MMP molecule(s)	Role in ovarian cancer
Pei et al., 2016 (²⁸28. Pei H, Yang Y, Cui L, Yang J, Li X, Yang Y, Duan H. Bisdemethoxycurcumin inhibits ovarian cancer via reducing oxidative stress mediated MMPs expressions. Sci Rep 2016; 6: 28773, doi: 10.1038/srep28773. https://doi.org/10.1038/srep28773... )	MMP-2 and MMP-9	Bisdemethoxycurcumin inhibits ovarian cancer cells via reducing oxidative stress-mediated expression of MMP-2 and -9.
Wang et al., 2016 (²⁷27. Wang J, Chen D, Li B, He J, Duan D, Shao D, et al. Fe-MIL-101 exhibits selective cytotoxicity and inhibition of angiogenesis in ovarian cancer cells via downregulation of MMP. Sci Rep 2016; 6: 26126, doi: 10.1038/srep26126. https://doi.org/10.1038/srep26126... )	MMP-2 and MMP-9	Fe-MIL-101 suppresses the proliferation of human SKOV3 ovarian cancer cells via downregulation the expression of MMP-2 and -9.
Vos et al., 2016 (³⁷37. Vos MC, Hollemans E, Ezendam N, Feijen H, Boll D, Pijlman B, et al. MMP-14 and CD44 in epithelial-to-mesenchymal transition (EMT) in ovarian cancer. J Ovarian Res 2016; 9: 53, doi: 10.1186/s13048-016-0262-7. https://doi.org/10.1186/s13048-016-0262-... )	MMP-14	Patients with double expression of MMP-14 and CD44 have a poor prognosis.
Fu et al., 2015 (¹¹11. Fu Z, Xu S, Xu Y, Ma J, Li J, Xu P. The expression of tumor-derived and stromal-derived matrix metalloproteinase 2 predicted prognosis ofovarian cancer. Int J Gynecol Cancer 2015; 25: 356–262, doi: 10.1097/IGC.0000000000000386. https://doi.org/10.1097/IGC.000000000000... )	MMP-2	Tumor-derived MMP-2 expression predicts a lower overall survival rate and could be an independent prognostic factor in patients with ovarian cancer.
Gonzalez-Villasana et al., 2015 (¹⁵15. Gonzalez-Villasana V, Fuentes-Mattei E, Ivan C, Dalton HJ, Rodriguez-Aguayo C, Fernandez-de-Thomas RJ, et al. Rac1/Pak1/p38/MMP-2 axis regulates angiogenesis in ovarian cancer. Clin Cancer Res, 2015; 21: 2127–2137, doi: 10.1158/1078-0432.CCR-14-2279. https://doi.org/10.1158/1078-0432.CCR-14... )	MMP-2	Zoledronic acid exerts robust inhibitory activity on cell invasion of HeyA8-MDR and OVCAR-5 ovarian cancer cells through decreasing the intracellular level of MMP-2.
Liu etal., 2015 (³³33. Liu L, Sun J, Li G, Gu B, Wang X, Chi H, et al. Association between MMP-12-82A/G polymorphism and cancer risk: a meta-analysis. Int J Clin Exp Med 2015; 8: 11896–11904.)	MMP-12	MMP-12 82 A/G polymorphism increases the susceptibility to ovarian cancer despite not being significantly associated with overall cancer risk.
Chen et al., 2015 (³²32. Chen SS, Song J, Tu XY, Zhao JH, Ye XQ. The association between MMP-12 82 A/G polymorphism and susceptibility to various malignant tumors: a meta-analysis. Int J Clin Exp Med 2015; 8: 10845–10854.)	MMP-12	MMP-12 82 A/G polymorphism is a genetic risk factor for epithelial ovarian carcinoma.
Gao et al., 2014 (¹⁴14. Gao N, Tian JX, Shang YH, Zhao DY, Wu T. Catalpol suppresses proliferation and facilitates apoptosis of OVCAR-3 ovarian cancer cells through upregulating microRNA-200 and downregulating MMP-2 expression. Int J Mol Sci 2014; 15: 19394–19405, doi: 10.3390/ijms151119394. https://doi.org/10.3390/ijms151119394... )	MMP-2	Catalpol suppresses proliferation and accelerated apoptosis of OVCAR-3 ovarian cancer cells via promoting microRNA-200 expression and reducing MMP-2 signaling.
Bandaru et al., 2014 (²⁶26. Bandaru S, Zhou AX, Rouhi P, Zhang Y, Bergo MO, Cao Y, et al. Targeting filamin B induces tumor growth and metastasis via enhanced activity of matrix metalloproteinase-9 and secretion of VEGF-A. Oncogenesis 2014; 3: e119, doi: 10.1038/oncsis.2014.33. https://doi.org/10.1038/oncsis.2014.33... )	MMP-9	Filamin B (FLNB) suppresses the growth and metastasis of human ovarian cancer by down-regulating the activity of MMP-9 and secretion of vascular endothelial growth factor-A (VEGF-A).
Trudel et al., 2014 (³⁶36. Trudel D, Desmeules P, Turcotte S, Plante M, Grégoire J, Renaud MC, et al. Visual and automated assessment of matrix metalloproteinase-14 tissue expression for the evaluation ofovarian cancer prognosis. Mod Pathol 2014; 27: 1394–1404, doi: 10.1038/modpathol.2014.32. https://doi.org/10.1038/modpathol.2014.3... )	MMP-14	Higher expression of MMP-14 is associated with lower progression and better prognosis of ovarian carcinoma.
Wang et al., 2013 (¹⁰10. Wang L, Jin X, Lin D, Liu Z, Zhang X, Lu Y, et al. Clinicopathologic significance of claudin-6, occludin, and matrix metalloproteinases-2 expression in ovarian carcinoma. Diagn Pathol 2013; 8: 190.)	MMP-2	MMP-2 plays a positive role in the invasion and metastasis of ovarian cancer.
Al-Alem et al., 2013 (³⁰30. Al-Alem LF, McCord LA, Southard RC, Kilgore MW, Curry TE Jr. Activation of the PKC pathway stimulates ovarian cancer cell proliferation, migration, and expression of MMP7 and MMP10. Biol Reprod 2013; 89: 73.)	MMP-7 and MMP-10	Targeted inhibition of MMP-7 and MMP-10 may provide potential ovarian cancer therapeutic strategy.
Li et al., 2013 (²⁵25. Li LN, Zhou X, Gu Y, Yan J. Prognostic value of MMP-9 in ovarian cancer: a meta-analysis. Asian Pac J Cancer Prev 2013; 14: 4107–4113, doi: 10.7314/APJCP.2013.14.7.4107. https://doi.org/10.7314/APJCP.2013.14.7.... )	MMP-9	Increased expression of MMP-9 is associated with poor prognosis in ovarian cancer.
Kaimal et al., 2013 (³⁸38. Kaimal R, Aljumaily R, Tressel SL, Pradhan RV, Covic L, Kuliopulos A, et al. Selective blockade of matrix metalloprotease-14 with a monoclonal antibody abrogates invasion, angiogenesis, and tumor growth in ovarian cancer. Cancer Res 2013; 73: 2457–2467, doi: 10.1158/0008-5472.CAN-12-1426. https://doi.org/10.1158/0008-5472.CAN-12... )	MMP-14	MMP-14-dependent invasion and metastasis is effectively inhibited by intraperitoneal administration of monoclonal MMP-14 antibody.
Zhao et al., 2012 (²¹21. Zhao H, Yang Z, Wang X, Zhang X, Wang M, Wang Y, et al. Triptolide inhibits ovarian cancer cell invasion by repression of matrix metalloproteinase 7 and 19 and upregulation of E-cadherin. Exp Mol Med 2012; 44: 633–641, doi: 10.3858/emm.2012.44.11.072. https://doi.org/10.3858/emm.2012.44.11.0... )	MMP-7	Triptolide inhibits the migration and invasion of ovarian cancer cells by suppression of MMP-7.
Chang et al., 2012 (¹⁹19. Chang MC, Chen CA, Chen PJ, Chiang YC, Chen YL, Mao TL, et al. Mesothelin enhances invasion of ovarian cancer by inducing MMP-7 through MAPK/ERK and JNK pathways. Biochem J 2012; 442: 293–302, doi: 10.1042/BJ20110282. https://doi.org/10.1042/BJ20110282... )	MMP-7	Mesothelin enhances ovarian cancer invasion by MMP-7 expression through the MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) and JNK (c-Jun N-terminal kinase) signal transduction pathways.
Ghosh et al., 2012 (³⁴34. Ghosh S, Basu M, Roy SS. ETS-1 protein regulates vascular endothelial growth factor-induced matrix metalloproteinase-9 and matrix metalloproteinase-13 expression in human ovarian carcinoma cell line SKOV-3. J Biol Chem 2012; 287: 15001–15015, doi: 10.1074/jbc.M111.284034. https://doi.org/10.1074/jbc.M111.284034... )	MMP-9 and MMP-13	Activation of PI3K/AKT (phosphatidylinositol-3-kinase) and p38 MAPK by VEGF activates MMP-9 and MMP-13, leading to the invasion of SKOV-3 cells.
Agarwal et al., 2010 (⁴4. Agarwal A, Tressel SL, Kaimal R, et al. Identification of a metalloprotease-chemokine signaling system in the ovarian cancer microenvironment: implications for antiangiogenic therapy. Cancer Res 2010; 70: 5880–5890, doi: 10.1158/0008-5472.CAN-09-4341. https://doi.org/10.1158/0008-5472.CAN-09... )	MMP-1	MMP-1-PAR1 (protease-activated receptor-1) activation induces secretion of several angiogenic factors in ovarian carcinoma cells, leading to cell proliferation, tube formation and migration.

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[1] Correspondence: Q. Chen: <shishan14606@sohu.com>