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Role of Metalloproteinases in Melanoma Growth and Progression

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Proteases in Human Diseases

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Abstract

Matrix metalloproteinases (MMPs) are zinc-containing endopeptidases with an extensive range of substrate specificities. Together, these enzymes are able to degrade various components of extracellular matrix (ECM) proteins and driven important physiological and pathological process, such as reproduction, wound healing, inflammation, and cancer development. In melanoma, MMPs are involved in growth, invasion, and metastasis process. In this disease, as in other tumors, the degradation of ECM permits angiogenesis and the migration of melanoma cells to distant sites. In this chapter, we focus on the functional characteristic of the main MMPs and their contributions to melanoma development.

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References

  1. Singh D, Srivastava SK, Chaudhuri TK et al (2015) Multifaceted role of matrix metalloproteinases (MMPs). Front Mol Biosci. doi:10.3389/fmolb.2015.00019

  2. Marco M, Fortin C, Fulop T (2013) Membrane-type matrix metalloproteinases: key mediators of leukocyte function. J Leukoc Biol 94:237–246

    Article  CAS  PubMed  Google Scholar 

  3. Amalinei C, Caruntu ID, Balan RA (2007) Biology of metalloproteinases. Rom J Morphol Embryol 48(4):323–334

    PubMed  Google Scholar 

  4. Pulkoski-Gross AE (2015) Historical perspective of matrix metalloproteinases. Front Biosci (Schol Ed) 7:125–149

    Article  Google Scholar 

  5. Moro N, Mauch C, Zigrino P (2015) Metalloproteinases in melanoma. Eur J Cell Biol 93:23–29

    Article  Google Scholar 

  6. Gross J, Lapiere CM (1962) Collagenolytic activity in amphibian tissues: a tissue culture assay. Proc Natl Acad Sci USA 48:1014–1022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Eisen AZ, Jeffrey JJ, Gross J (1968) Human skin collagenase. Isolation and mechanism of attack on the collagen molecule. Biochim Biophys Acta 151:637–645

    Article  CAS  PubMed  Google Scholar 

  8. Lopez-Otin C, Palavalli LH, Samuels Y (2009) Protective roles of matrix metalloproteinases: from mouse models to human cancer. Cell Cycle 8:3657–3662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Parks MC, Wilson CL, López-Boado YS (2004) Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev Immunol 4:617–629

    Article  CAS  PubMed  Google Scholar 

  10. Page-McCaw A, Ewald AJ, Werb Z (2007) Matrix metalloproteinases and the regulation of tissue remodeling. Nat Rev Mol Cell Biol 8:221–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Van Wart HE, Birkedal-Hansen H (1990) The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family. Proc Natl Acad Sci USA 87:5578–5582

    Article  PubMed  PubMed Central  Google Scholar 

  12. Moore CS, Crocker SJ (2012) An alternative perspective on the roles of TIMPs and MMPs in pathology. Am J Pathol 180:12–16

    Article  CAS  PubMed  Google Scholar 

  13. Arpino V, Brock M, Gill SE (2015) The role of TIMPs in regulation of extracellular matrix proteolysis. Matrix Biol 44–46:247–254

    Article  PubMed  Google Scholar 

  14. Kessenbrock K, Plaks V, Werb Z (2010) Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141:52–67

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Jung KK, Liu XW, Chirco R, Fridman R, Kim HRC (2006) Identification of CD63 as a tissue inhibitor of metalloproteinase-1 interacting cell surface protein. EMBO J 25:3934–3942

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Toricelli M, Melo F, Peres G (2013) Timp1 interacts with beta-1 integrin and CD63 along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway independently of Akt phosphorylation. Mol Cancer 12:1–15

    Article  Google Scholar 

  17. McCawley LJ, Matrisian LM (2001) Matrix metalloproteinases: they’re not just for matrix anymore! Curr Opin Cell Biol 13:534–540

    Article  CAS  PubMed  Google Scholar 

  18. Selman M, Ruiz V, Cabrera S et al (2000) TIMP-1, -2, -3, and -4 in idiopathic pulmonary fibrosis. A prevailing nondegradative lung microenvironment? Am J Physiol Lung Cell Mol Physiol 279:562–574

    Google Scholar 

  19. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2:161–174

    Article  CAS  PubMed  Google Scholar 

  21. Dye D, Medic S, Ziman M et al (2013) Melanoma biomolecules: independently identified but functionally interwined. Front Oncol. doi:10.3389/fonc.2013.00252

    PubMed  PubMed Central  Google Scholar 

  22. Sullivan R, LoRusso P, Boerner S et al (2015) Achievements and challenges of molecular targeted therapy in melanoma. Am Soc Clin Oncol Educ Book 2015:177–186. doi:10.14694/EdBook_AM.2015.35.177

    Article  Google Scholar 

  23. Cowden Dahl KD, Symowicz J, Ning Y et al (2008) Matrix metalloproteinase 9 is a mediator of epidermal growth factor-dependent e-cadherin loss in ovarian carcinoma cells. Cancer Res 68:4606–4613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Radisky DC, Levy DD, Littlepage LE et al (2005) Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature 436:123–127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Mitsiades N, Yu WH, Poulaki V et al (2001) Matrix metalloproteinase-7-mediated cleavage of Fas ligand protects tumor cells from chemotherapeutic drug cytotoxicity. Cancer Res 61:577–581

    CAS  PubMed  Google Scholar 

  26. Liu H, Zhang T, Li X et al (2008) Predictive value of MMP-7 expression for response to chemotherapy and survival in patients with non-small cell lung cancer. Cancer Sci 99:2185–2192

    Article  CAS  PubMed  Google Scholar 

  27. Yu Q, Stamenkovic I (2000) Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev 14:163–176

    PubMed  PubMed Central  Google Scholar 

  28. Mu D, Cambier S, Fjellbirkeland L et al (2002) The integrin alpha(v)beta8 mediates epithelial homeostasis through MT1-MMP-dependent activation of TGF-beta1. J Cell Biol 157:493–507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Van Wart H, Birkedal-Hansen HH (1990) The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family. Proc Natl Acad Sci 87:5578–5582

    Article  PubMed  PubMed Central  Google Scholar 

  30. Rodriguez D, Morrison C (1803) Overall C matrix metalloproteinases: what do they not do? New substrates and biological roles identified by murine models and proteomics. Biochim Biophys Acta 39–54:2010

    Google Scholar 

  31. Ribeiro R, Borges Junior P, Cardoso S et al (2008) Expression of matrix metalloproteinasis and their tissue inhibitors in basal cell carcinoma. J Bras Patol Med Lab 44:115–121

    Article  CAS  Google Scholar 

  32. Lugowska I, Kowalska M, Fuksiewicz M et al (2015) Serum markers in early-stage and locally advanced melanoma. Tumour Biol 36:8277–8285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Itoh T, Tanioka M, Matsuda H et al (1999) Experimental metastasis is suppressed in MMP-9-deficient mice. Clin Exp Met 17:177–181

    Article  CAS  Google Scholar 

  34. Kaplan RN, Riba RD, Zacharoulis S et al (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438:820–827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Boire A, Covic L, Agarwal A et al (2005) PAR-1 is a matrix metalloprotease-I receptor that promotes invasion and tumorigenesis of breast cancer cells. Cell 120:303–313

    Article  CAS  PubMed  Google Scholar 

  36. Lynch CC, Hikosaka A, Acuff HB et al (2005) MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL. Cancer Cell 7:485–496

    Article  CAS  PubMed  Google Scholar 

  37. Reed MJ, Corsa AC, Kudravi SA et al (2000) A deficit in collagenase activity contributes to impaired migration of aged microvascular endothelial cells. J Cell Biochem 77:116–126

    Article  CAS  PubMed  Google Scholar 

  38. O’Grady A, Dunne C, O’Kelly P et al (2007) Differential expression of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in non-melanoma skin cancer: implications for tumour progression. Histopathology 51:793–798

    Article  PubMed  Google Scholar 

  39. Quan T, Qin Z, Xia W et al (2009) Matrix-degrading metalloproteinases in photoaging. J Investig Dermatol Symp Proc 14:20–24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Pittayapruek P, Meephansan J, Prapagan O et al (2016) Role of matrix metalloproteinases in photoaging and photocarcinogenesis. Int J Mol Sci 17(6):868

    Article  PubMed Central  Google Scholar 

  41. Mahabeleshwar G, Byzova T (2007) Angiogenesis in melanoma. Semin Oncol 34:555–565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Rudek M, Figg W, Dyer V et al (2001) Phase I clinical trial of oral COL-3, a matrix metalloproteinase inhibitor, in patients with refractory metastatic cancer. J Clin Oncol 19:584–592

    Article  CAS  PubMed  Google Scholar 

  43. Nikkola J, Vihinen P, Vuoristo M et al (2005) High serum levels of matrix metalloproteinase-9 and matrix metalloproteinase-1 are associated with rapid progression in patients with metastatic melanoma. Clin Cancer Res 11:5158–5166

    Article  CAS  PubMed  Google Scholar 

  44. Väisänen AH, Kallioinen M, Turpeenniemi-Hujanen T (2008) Comparison of the prognostic value of matrix metalloproteinases 2 and 9 in cutaneous melanoma. Hum Pathol 39:377–385

    Article  PubMed  Google Scholar 

  45. Ria R, Reale A, Castrovilli A et al (2010) Angiogenesis and progression in human melanoma. Dermatol Res Pract 2010. ID 185687 doi:10.1155/2010/185687

  46. Hashizume K (2007) Analysis of utero-placental-specific molecules and their functions during implantation and placentation in the bovine. J Reprod Dev 53:1–11

    Article  CAS  PubMed  Google Scholar 

  47. Rotte A, Martinka M, Li G (2012) MMP-2 expression is a prognostic marker for primary melanoma patients. Cell Oncol 35:207–216

    Article  CAS  Google Scholar 

  48. JiaoY Feng X, Zhan Y et al (2012) Matrix metalloproteinase-2 promotes alphavbeta3 integrin-mediated adhesion and migration of human melanoma cells by cleaving fibronectin. PLoS ONE 7:e41591

    Article  Google Scholar 

  49. Iida J, Wilhelmson K, Price M et al (2004) Membrane type-1 matrix metalloproteinase promotes human melanoma invasion and growth. J Invest Dermatol 122:167–176

    Article  CAS  PubMed  Google Scholar 

  50. Schnaeker EM, Ossig R, Ludwig T et al (2004) Microtubule-dependent matrix metalloproteinase-2/matrix metalloproteinase-9 exocytosis: prerequisite in human melanoma cell invasion. Cancer 64:8924–8931

    CAS  Google Scholar 

  51. Cotignola J, Reva B, Mitra N et al (2007) Matrix metalloproteinase-9 (MMP-9) polymorphisms in patients with cutaneous malignant melanoma. BMC Med Genet 8:10. doi:10.1186/1471-2350-8-10

    Article  PubMed  PubMed Central  Google Scholar 

  52. Farina A, Mackay A (2014) Gelatinase B/MMP-9 in tumour pathogenesis and progression. Cancers (Basel) 6(1):240–296

    Article  Google Scholar 

  53. Airola K, Karonen T, Vaalamo M et al (1999) Expression of collagenases-1 and -3 and their inhibitors TIMP-1 and -3 correlates with the level of invasion in malignant melanomas. Br J Cancer 80:733–743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Wandel E, Grasshoff A, Mittag M et al (2000) Fibroblasts surrounding melanoma express elevated levels of matrix metalloproteinase-1 (MMP-1) and intercellular adhesion molecule-1 (ICAM-1) in vitro. Exp Dermatol 9:34–41

    Article  CAS  PubMed  Google Scholar 

  55. Zigrino P, Kuhn I, Bauerle T et al (2009) Stromal expression of MMP-13 is required for melanoma invasion and metastasis. J Invest Dermatol 129:2686–2693

    Article  CAS  PubMed  Google Scholar 

  56. Lederle W, Hartenstein B, Meides A et al (2010) MMP-13 as a stromal mediator in controlling persistent angiogenesis in skin carcinoma. Carcinogenesis 31(7):1175–1184

    Article  CAS  PubMed  Google Scholar 

  57. Balbin M, Fueyo A, Tester AM et al (2003) Loss of collagenase-2 confers increased skin tumor susceptibility to male mice. Nat Genet 35:252–257

    Article  CAS  PubMed  Google Scholar 

  58. Gutierrez-Fernandez A, Fueyo A, Folgueras AR et al (2008) Matrix metalloproteinase-8 functions as a metastasis suppressor through modulation of tumor cell adhesion and invasion. Cancer Res 68:2755–2763

    Article  CAS  PubMed  Google Scholar 

  59. Vlaykova T, Kurzawski M, Tacheva T et al (2014) Investigation of the role of MMP3-1171insA polymorphism in cutaneous malignant melanoma a preliminary study. Biotechnol Biotechnl Equip 28:904–910

    Article  CAS  Google Scholar 

  60. De Oliveira Poswar F, de Carvalho Fraga CA, Gomes ESB et al (2015) Protein expression of MMP-2 and MT1-MMP in actinic keratosis, squamous cell carcinoma of the skin, and basal cell carcinoma. Int J Surg Pathol 23:20–25

    Article  Google Scholar 

  61. Oh ST, Kim HS, Yoo NJ et al (2011) Increased immunoreactivity of membrane type-1 matrix metalloproteinase (MT1-MMP) and b-catenin in high-risk basal cell carcinoma. Br Assoc Dermatol 165:1197–1204

    Article  CAS  Google Scholar 

  62. Tatti O, Arjama M, Ranki A et al (2011) Membrane-type-3 matrix metalloproteinase (MT3-MMP) functions as a matrix composition-dependent effector of melanoma cell invasion. PLoS ONE 6:1–13

    Article  Google Scholar 

  63. Tewari A, Grys K, Kollet J et al (2014) Upregulation of MMP-12 and its activity by UVA1 in human skin: potential implications for photoaging. J Investig Dermatol 134:2598–2609

    Article  CAS  PubMed  Google Scholar 

  64. Taddese S, Weiss AS, Jahreis G et al (2009) In vitro degradation of human tropoelastin by MMP-12 and the generation of matrikines from domain 24. Matrix Biol 28:84–91

    Article  CAS  PubMed  Google Scholar 

  65. Zhang Z, Zhu S, Yang Y et al (2015) Matrix metalloproteinase-12 expression is increased in cutaneous melanoma and associated with tumor aggressiveness. Tumor Biol 36:8593–8600

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Presidente Antonio Carlos, 6627 – Pampulha, Belo Horizonte, MG, CEP 31270-901, Brazil

    Cinthia Figueiredo & Ana Candida Araujo e Silva

  2. Faculdade de Medicina do Mucuri, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Rua do Cruzeiro, 01 – Jardim São Paulo, Teófilo Otoni, MG, CEP 39803-371, Brazil

    Cinthia Figueiredo & Ana Candida Araujo e Silva

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  1. Cinthia Figueiredo
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  2. Ana Candida Araujo e Silva
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Correspondence to Cinthia Figueiredo .

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Editors and Affiliations

  1. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Tapati Chakraborti

  3. Department of Physiology, Faculty of Medicine, St. Boniface General Hospital, Institute of Cardiovascular Sciences, University of Manitoba, Winnipeg, Manitoba, Canada

    Naranjan S. Dhalla

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Figueiredo, C., Araujo e Silva, A.C. (2017). Role of Metalloproteinases in Melanoma Growth and Progression. In: Chakraborti, S., Chakraborti, T., Dhalla, N. (eds) Proteases in Human Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-10-3162-5_5

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