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Role of meprin metalloproteases in metastasis and tumor microenvironment

  • Florian Peters
  • Christoph Becker-PaulyEmail author
Article

Abstract

A crucial step for tumor cell extravasation and metastasis is the migration through the extracellular matrix, which requires proteolytic activity. Hence, proteases, particularly matrix metalloproteases (MMPs), have been discussed as therapeutic targets and their inhibition should diminish tumor growth and metastasis. The metalloproteases meprin α and meprin β are highly abundant on intestinal enterocytes and their expression was associated with different stages of colorectal cancer. Due to their ability to cleave extracellular matrix (ECM) components, they were suggested as pro-tumorigenic enzymes. Additionally, both meprins were shown to have pro-inflammatory activity by cleaving cytokines and their receptors, which correlates with chronic intestinal inflammation and associated conditions. On the other hand, meprin β was identified as an essential enzyme for the detachment and renewal of the intestinal mucus, important to prevent bacterial overgrowth and infection. Considering this, it is hard to estimate whether high activity of meprins is generally detrimental or if these enzymes have also protective functions in certain cancer types. For instance, for colorectal cancer, patients with high meprin β expression in tumor tissue exhibit a better survival prognosis, which is completely different to prostate cancer. This demonstrates that the very same enzyme may have contrary effects on tumor initiation and growth, depending on its tissue and subcellular localization. Hence, precise knowledge about proteolytic enzymes is required to design the most efficient therapeutic options for cancer treatment. In this review, we summarize the current findings on meprins’ functions, expression, and cancer-associated variants with possible implications for tumor progression and metastasis.

Keywords

Metalloprotease Meprin ADAM Astacin Ectodomain shedding Inhibition 

Notes

Acknowledgments

This work was supported by the Deutsche Forschungsgemeinschaft (DFG) Project-number 125440785 SFB 877 (Proteolysis as a Regulatory Event in Pathophysiology, Projects A9 and A15) and BE 4086/2-2 (C.B.-P.).

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Unit for Degradomics of the Protease Web, Biochemical InstituteUniversity of KielKielGermany

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