Department of Applied Clinical and Biotechnological Sciences, University of L'Aquila, Via Vetoio, Coppito 2, L'Aquila 67100, Italy.
Cancers (Basel). 2014 Jan 27;6(1):240-96. doi: 10.3390/cancers6010240.
Since its original identification as a leukocyte gelatinase/type V collagenase and tumour type IV collagenase, gelatinase B/matrix metalloproteinase (MMP)-9 is now recognised as playing a central role in many aspects of tumour progression. In this review, we relate current concepts concerning the many ways in which gelatinase B/MMP-9 influences tumour biology. Following a brief outline of the gelatinase B/MMP-9 gene and protein, we analyse the role(s) of gelatinase B/MMP-9 in different phases of the tumorigenic process, and compare the importance of gelatinase B/MMP-9 source in the carcinogenic process. What becomes apparent is the importance of inflammatory cell-derived gelatinase B/MMP-9 in tumour promotion, early progression and triggering of the "angiogenic switch", the integral relationship between inflammatory, stromal and tumour components with respect to gelatinase B/MMP-9 production and activation, and the fundamental role for gelatinase B/MMP-9 in the formation and maintenance of tumour stem cell and metastatic niches. It is also apparent that gelatinase B/MMP-9 plays important tumour suppressing functions, producing endogenous angiogenesis inhibitors, promoting inflammatory anti-tumour activity, and inducing apoptosis. The fundamental roles of gelatinase B/MMP-9 in cancer biology underpins the need for specific therapeutic inhibitors of gelatinase B/MMP-9 function, the use of which must take into account and substitute for tumour-suppressing gelatinase B/MMP-9 activity and also limit inhibition of physiological gelatinase B/MMP-9 function.
自从最初被鉴定为白细胞明胶酶/IV 型胶原酶和肿瘤 IV 型胶原酶以来，明胶酶 B/基质金属蛋白酶（MMP）-9 现在被认为在肿瘤进展的许多方面发挥着核心作用。在这篇综述中，我们将阐述当前关于明胶酶 B/MMP-9 影响肿瘤生物学的多种方式的概念。在简要概述明胶酶 B/MMP-9 基因和蛋白质之后，我们分析了明胶酶 B/MMP-9 在肿瘤发生过程的不同阶段的作用，并比较了明胶酶 B/MMP-9 在致癌过程中的来源的重要性。显而易见的是，炎性细胞衍生的明胶酶 B/MMP-9 在肿瘤促进、早期进展和触发“血管生成开关”中的重要性，炎性、基质和肿瘤成分之间在明胶酶 B/MMP-9 产生和激活方面的内在关系，以及明胶酶 B/MMP-9 在肿瘤干细胞和转移灶形成和维持中的基本作用。同样明显的是，明胶酶 B/MMP-9 具有重要的肿瘤抑制功能，产生内源性血管生成抑制剂，促进炎症抗肿瘤活性，并诱导细胞凋亡。明胶酶 B/MMP-9 在癌症生物学中的基本作用突显了对明胶酶 B/MMP-9 功能的特异性治疗抑制剂的需求，在使用这些抑制剂时必须考虑并替代肿瘤抑制型明胶酶 B/MMP-9 活性，并限制对生理明胶酶 B/MMP-9 功能的抑制。
