Matrix Metalloproteinase-8 functions as a metastasis suppressor through modulation of tumour cell adhesion and invasion

Gutierrez-Fernandez, Ana, Fueyo, Antonio, Folgueras, Alicia R., Garabaya, Cecilia, Pennington, Caroline J., Pilgrim, Simon, Edwards, Dylan R. ORCID:, Holliday, Deborah L., Jones, J. Louise, Span, Paul N., Sweep, Fred C. G. J., Puente, Xose S. and López-Otín, Carlos (2008) Matrix Metalloproteinase-8 functions as a metastasis suppressor through modulation of tumour cell adhesion and invasion. Cancer Research, 68 (8). pp. 2755-2763.

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Collagenase-2 (matrix metalloproteinase-8, MMP-8) is an MMP mainly produced by neutrophils and associated with many inflammatory conditions. We have previously described that MMP-8 plays a protective role in cancer through its ability to regulate the inflammatory response induced by carcinogens. Moreover, it has been reported that experimental manipulation of the expression levels of this enzyme alters the metastatic behavior of human breast cancer cells. In this work, we have used mutant mice deficient in MMP-8 and syngenic melanoma and lung carcinoma tumor cells lines overexpressing this enzyme to further explore the putative antimetastatic potential of MMP-8. We report herein that MMP-8 prevents metastasis formation through the modulation of tumor cell adhesion and invasion. Thus, tumor cells overexpressing MMP-8 have an increased adhesion to extracellular matrix proteins, whereas their invasive ability through Matrigel is substantially reduced when compared with control cells. Analysis of MMP-8 in breast cancer patients revealed that the expression of this metalloproteinase by breast tumors correlates with a lower incidence of lymph node metastasis and confers good prognosis to these patients. On this basis, we propose that MMP-8 is a tumor protective factor, which also has the ability to reduce the metastatic potential of malignant cells in both mice and human. [Cancer Res 2008;68(8):2755–63]

Item Type: Article
Uncontrolled Keywords: sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Science > School of Biological Sciences
UEA Research Groups: Faculty of Science > Research Groups > Cells and Tissues
Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies
Depositing User: EPrints Services
Date Deposited: 01 Oct 2010 13:38
Last Modified: 22 Apr 2023 00:59
DOI: 10.1158/0008-5472.CAN-07-5154

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