The 72-kDa type IV collagenase or gelatinase A is the second member of the matrix metalloproteinase family, MMP-2. Since the discovery of its first two substrates within components of the extracellular matrix, denatured interstitial type I collagen and native type IV collagen, the roles and various levels of regulation of MMP-2 have been intensively studied, mainly in vitro. Its (over)expression in most if not all tumors was considered a hallmark of cancer aggressiveness and boosted investigations aiming at its inhibition. Unfortunately, the enthusiasm subsided like a soufflé after clinical trial failures, mostly because of insufficient knowledge of in vivo MMP-2 activities and detrimental side effects of broad-spectrum MMP inhibition. Nowadays, MMP-2 remains a major topic of interest in research, the second in the MMP family after MMP-9. This review presents a broad overview of the major features of this protease. This knowledge is crucial to identify diagnostic or therapeutic strategies focusing on MMP-2. In this sense, recent publications and clinical trials underline the potential value of measuring circulating or tissular MMP-2 levels as diagnostic or prognostic tools, or as a useful secondary outcome for therapies against other primary targets. Direct MMP-2 inhibition has benefited from substantial progress in the design of more specific inhibitors but their in vivo application remains challenging but certainly worth the efforts it receives.

中文翻译：

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基质金属蛋白酶2 ：（过去）不是过去的“英雄”。

72 kDa的IV型胶原酶或明胶酶A是基质金属蛋白酶家族MMP-2的第二个成员。自从在细胞外基质，变性的间质I型胶原和天然IV型胶原的成分中发现其前两个底物以来，就对MMP-2的作用和各种水平的调节进行了深入研究，主要是在体外。在大多数（如果不是全部）肿瘤中，其（过度）表达被认为是癌症侵袭性的标志，并加强了针对其抑制作用的研究。不幸的是，在临床试验失败后，热情像糖果般消退，这主要是由于对体内MMP-2活性的了解不足以及广谱MMP抑制的有害副作用。如今，MMP-2仍是研究中的主要话题，在MMP家族中仅次于MMP-9。这篇综述对这种蛋白酶的主要特征进行了广泛的概述。这些知识对于确定专注于MMP-2的诊断或治疗策略至关重要。从这个意义上讲，最近的出版物和临床试验强调了测量循环或组织MMP-2水平作为诊断或预后工具，或作为针对其他主要靶标治疗的有用辅助结果的潜在价值。直接MMP-2抑制已受益于更特异性抑制剂设计的实质性进展，但其体内应用仍然具有挑战性，但无疑值得其努力。最近的出版物和临床试验强调了测量循环或组织MMP-2水平作为诊断或预后工具，或作为针对其他主要靶点的治疗的有用辅助结果的潜在价值。直接MMP-2抑制已受益于更特异性抑制剂的设计的实质性进展，但它们在体内的应用仍然具有挑战性，但肯定值得其努力。最近的出版物和临床试验强调了测量循环或组织MMP-2水平作为诊断或预后工具，或作为针对其他主要靶点的治疗的有用辅助结果的潜在价值。直接MMP-2抑制已受益于更特异性抑制剂的设计的实质性进展，但它们在体内的应用仍然具有挑战性，但肯定值得其努力。