The Role of the Metzincin Superfamily in Prostate Cancer Progression: A Systematic-Like Review.

Marley J Binder,Alister C Ward

doi:10.3390/ijms22073608

Abstract

Prostate cancer remains a leading cause of cancer-related morbidity in men. Potentially important regulators of prostate cancer progression are members of the metzincin superfamily of proteases, principally through their regulation of the extracellular matrix. It is therefore timely to review the role of the metzincin superfamily in prostate cancer and its progression to better understand their involvement in this disease. A systematic-like search strategy was conducted. Articles that investigated the roles of members of the metzincin superfamily and their key regulators in prostate cancer were included. The extracted articles were synthesized and data presented in tabular and narrative forms. Two hundred and five studies met the inclusion criteria. Of these, 138 investigated the role of the Matrix Metalloproteinase (MMP) subgroup, 34 the Membrane-Tethered Matrix Metalloproteinase (MT-MMP) subgroup, 22 the A Disintegrin and Metalloproteinase (ADAM) subgroup, 8 the A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS) subgroup and 53 the Tissue Inhibitor of Metalloproteinases (TIMP) family of regulators, noting that several studies investigated multiple family members. There was clear evidence that specific members of the metzincin superfamily are involved in prostate cancer progression, which can be either in a positive or negative manner. However, further understanding of their mechanisms of action and how they may be used as prognostic indicators or molecular targets is required.

Highlights

Prostate cancer (PrCa) is one of the major causes of cancer-related morbidity in men worldwide [1,2]
This identified 205 articles that are presented in five tables, each covering a specific subgroup of the metzincin superfamily or their regulators—the Matrixin family subgroups Matrix Metalloproteinase (MMP) and Membrane-Tethered Matrix Metalloproteinase (MT-MMP), the Tissue Inhibitor of Metalloproteinases (TIMP) and the Adamalysin family subgroups A Disintegrin and Metalloproteinase (ADAM) and A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTSs)
This study used a systematic-like review strategy to identify publications examining the role of metzincins in PrCa progression

Summary

Introduction

Prostate cancer (PrCa) is one of the major causes of cancer-related morbidity in men worldwide [1,2]. The early stages of PrCa are androgen-dependent, but during PrCa progression, the tumors become independent of androgens [1,3]. The detection of PrCa is difficult, with symptoms often not being apparent until metastasis has occurred [1]. The use of the Prostate-Specific Antigen (PSA) test is considered a gold standard, yet remains flawed, with a considerable false-positive rate [1,4]. The survival rates for men diagnosed with PrCa have increased, the treatment options can have significant side effects [1,2]. An increased understanding of the etiology of this disease provides the potential to develop more specific detection methods and/or alternative treatment modalities

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