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Matrix metalloproteinase 2 attenuates brain tumour growth, while promoting macrophage recruitment and vascular repair
Author(s) -
Tremblay Pierrot,
Beaudet MarieJosée,
Tremblay Eve,
Rueda Naika,
Thomas Tina,
Vallières Luc
Publication year - 2011
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2854
Subject(s) - mmp2 , cancer research , astrocytoma , matrix metalloproteinase , biology , extracellular matrix , pathology , cell culture , cell growth , downregulation and upregulation , glioma , microbiology and biotechnology , medicine , gene , biochemistry , genetics
Matrix metalloproteinase 2 (MMP2) is an extracellular protein‐degrading enzyme widely believed to be involved in the invasion of brain tumour cells. However, this assumption is mainly based on in vitro studies. By characterizing the transcriptome and in vivo properties of 20 astrocytoma cell lines, we found that the levels of MMP2 were higher in GFAP − astrocytoma cells and correlated with their ability to induce vascular changes, a common complication of malignant tumours. To study the relationship between MMP2 expression and vascular alteration, we intracerebrally implanted immunodeficient mice with human astrocytoma cells stably transduced with lentiviral vectors expressing either MMP2 or a short hairpin RNA against MMP2. We found that the tumours depleted of MMP2 were larger, contained more proliferating cells and fewer macrophages, and had a vasculature that was more destabilized and regressed with fewer capillary sprouts. In contrast, the tumours overexpressing MMP2 were smaller and showed no histological difference compared to the controls. We therefore suggest that MMP2 is not the cause of vascular atypia in malignant brain tumours, but is involved in a tissue repair response that tends to limit the growth of these tumours. This study argues against MMP2 inhibition as a therapeutic approach for brain cancer and provides a comprehensive characterization of popular astrocytoma cell lines that should help to identify alternative targets. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.