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Matrix Metalloproteases in Pancreatic Ductal Adenocarcinoma: Key Drivers of Disease Progression?

1
Center of Experimental and Molecular Medicine, University of Amsterdam, Amsterdam UMC, 1105 AZ Amsterdam, The Netherlands
2
Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, University of Amsterdam, Amsterdam UMC, 1105 AZ Amsterdam, The Netherlands
3
Oncode Institute, 1105 AZ Amsterdam, The Netherlands
*
Author to whom correspondence should be addressed.
Biology 2020, 9(4), 80; https://doi.org/10.3390/biology9040080
Received: 26 March 2020 / Revised: 15 April 2020 / Accepted: 15 April 2020 / Published: 18 April 2020
Pancreatic cancer is a dismal disorder that is histologically characterized by a dense fibrotic stroma around the tumor cells. As the extracellular matrix comprises the bulk of the stroma, matrix degrading proteases may play an important role in pancreatic cancer. It has been suggested that matrix metalloproteases are key drivers of both tumor growth and metastasis during pancreatic cancer progression. Based upon this notion, changes in matrix metalloprotease expression levels are often considered surrogate markers for pancreatic cancer progression and/or treatment response. Indeed, reduced matrix metalloprotease levels upon treatment (either pharmacological or due to genetic ablation) are considered as proof of the anti-tumorigenic potential of the mediator under study. In the current review, we aim to establish whether matrix metalloproteases indeed drive pancreatic cancer progression and whether decreased matrix metalloprotease levels in experimental settings are therefore indicative of treatment response. After a systematic review of the studies focusing on matrix metalloproteases in pancreatic cancer, we conclude that the available literature is not as convincing as expected and that, although individual matrix metalloproteases may contribute to pancreatic cancer growth and metastasis, this does not support the generalized notion that matrix metalloproteases drive pancreatic ductal adenocarcinoma progression. View Full-Text
Keywords: MMP; MMP2; MMP9; MMP7; MMP14; matrix metalloproteases; PDAC; pancreatic cancer MMP; MMP2; MMP9; MMP7; MMP14; matrix metalloproteases; PDAC; pancreatic cancer
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Slapak, E.J.; Duitman, J.; Tekin, C.; Bijlsma, M.F.; Spek, C.A. Matrix Metalloproteases in Pancreatic Ductal Adenocarcinoma: Key Drivers of Disease Progression? Biology 2020, 9, 80.

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