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Gelatinase B/MMP-9 in Tumour Pathogenesis and Progression
Department of Applied Clinical and Biotechnological Sciences, University of L'Aquila, Via Vetoio, Coppito 2, L'Aquila 67100, Italy
* Author to whom correspondence should be addressed.
Received: 16 December 2013; in revised form: 20 January 2014 / Accepted: 21 January 2014 / Published: 27 January 2014
Abstract: 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.
Keywords: gelatinase B/MMP-9; tumour progression; angiogenesis; metastasis; inflammation; epithelial-mesenchymal transition; invasion; motility; immune surveillance; gelatinase B/MMP-9 inhibitors
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Farina, A.R.; Mackay, A.R. Gelatinase B/MMP-9 in Tumour Pathogenesis and Progression. Cancers 2014, 6, 240-296.
Farina AR, Mackay AR. Gelatinase B/MMP-9 in Tumour Pathogenesis and Progression. Cancers. 2014; 6(1):240-296.
Farina, Antonietta R.; Mackay, Andrew R. 2014. "Gelatinase B/MMP-9 in Tumour Pathogenesis and Progression." Cancers 6, no. 1: 240-296.