Details

Autor(en) / Beteiligte

• Gutiérrez-Fernández, Ana
• Fueyo, Antonio
• Folgueras, Alicia R
• Garabaya, Cecilia
• Pennington, Caroline J
• Pilgrim, Simon
• Edwards, Dylan R
• Holliday, Deborah L
• Jones, J Louise
• Span, Paul N
• Sweep, Fred C G J
• Puente, Xose S
• López-Otín, Carlos

Titel

Matrix metalloproteinase-8 functions as a metastasis suppressor through modulation of tumor cell adhesion and invasion

Ist Teil von

• Cancer research (Chicago, Ill.), 2008-04, Vol.68 (8), p.2755-2763

Ort / Verlag

United States

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.