The Role of MMP8 in Cancer: A Systematic Review

Int J Mol Sci. 2019 Sep 11;20(18):4506. doi: 10.3390/ijms20184506.

Krista Juurikka ¹ ², Georgina S Butler ³ ⁴, Tuula Salo ⁵ ⁶ ⁷ ⁸ ⁹, Pia Nyberg ¹⁰ ¹¹ ¹², Pirjo Åström ¹³ ¹⁴ ¹⁵ ¹⁶

Affiliations

1 Cancer and Translational Medicine Research Unit, Faculty of Medicine, University of Oulu, 90014 Oulu, Finland. [email protected].
2 Medical Research Center Oulu, Oulu University Hospital and University of Oulu, 90220 Oulu, Finland. [email protected].
3 Department of Oral Biological & Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, BC V6T 1Z2, Canada. [email protected].
4 Centre for Blood Research, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. [email protected].
5 Cancer and Translational Medicine Research Unit, Faculty of Medicine, University of Oulu, 90014 Oulu, Finland. [email protected].
6 Medical Research Center Oulu, Oulu University Hospital and University of Oulu, 90220 Oulu, Finland. [email protected].
7 Department of Oral and Maxillofacial Diseases, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland. [email protected].
8 Helsinki University Hospital, 00014 Helsinki, Finland. [email protected].
9 Translational Immunology Research Program (TRIMM), University of Helsinki, 00014 Helsinki, Finland. [email protected].
10 Cancer and Translational Medicine Research Unit, Faculty of Medicine, University of Oulu, 90014 Oulu, Finland. [email protected].
11 Medical Research Center Oulu, Oulu University Hospital and University of Oulu, 90220 Oulu, Finland. [email protected].
12 Biobank Borealis of Northern Finland, Oulu University Hospital, 90220 Oulu, Finland. [email protected].
13 Cancer and Translational Medicine Research Unit, Faculty of Medicine, University of Oulu, 90014 Oulu, Finland. [email protected].
14 Medical Research Center Oulu, Oulu University Hospital and University of Oulu, 90220 Oulu, Finland. [email protected].
15 Department of Oral Biological & Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, BC V6T 1Z2, Canada. [email protected].
16 Centre for Blood Research, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. [email protected].

PMID: 31514474 DOI: 10.3390/ijms20184506

Abstract

Matrix Metalloproteinases (MMPs) have traditionally been considered as tumor promoting Enzymes as they degrade extracellular matrix components, thus increasing the invasion of Cancer cells. It has become evident, however, that MMPs can also cleave and alter the function of various non-matrix bioactive molecules, leading to both tumor promoting and suppressive effects. We applied systematic review guidelines to study MMP8 in Cancer including the use of MMP8 as a prognostic factor or as a target/anti-target in Cancer treatment, and its molecular mechanisms. A total of 171 articles met the inclusion criteria. The collective evidence reveals that in breast, skin and oral tongue Cancer, MMP8 inhibits Cancer cell invasion and proliferation, and protects patients from metastasis via cleavage of non-structural substrates. Conversely, in liver and gastric cancers, high levels of MMP8 worsen the prognosis. Expression and genetic alterations of MMP8 can be used as a prognostic factor by examination of the tumor and serum/plasma. We conclude, that MMP8 has differing effects on cancers depending on their tissue of origin. The use of MMP8 as a prognostic factor alone, or with Other factors, seems to have potential. The molecular mechanisms of MMP8 in Cancer further emphasize its role as an important regulator of bioactive molecules.

Keywords

cancer; cancer drug therapy; matrix metalloproteinase 8; molecular mechanism; prognosis; systematic review.

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