title: Matrix metalloproteinase 2 attenuates brain tumour growth, while promoting macrophage recruitment and vascular repair.
abstract: 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.
authors.affiliation: Department of Endocrinology and Genomics, Laval University Hospital Research Center, Quebec, QC, Canada G1V 4G2.
authors.forename: Pierrot
authors.initials: P
authors.lastname: Tremblay
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Beaudet
authors.forename: Eve
authors.initials: E
authors.lastname: Tremblay
authors.forename: Naika
authors.initials: N
authors.lastname: Rueda
authors.forename: Tina
authors.initials: T
authors.lastname: Thomas
authors.forename: Luc
authors.initials: L
authors.lastname: Vallières
mesh_terms: D000818:Animals; D001254:Astrocytoma / Q000098:blood supply / Q000201:enzymology / Q000473:pathology*; D001932:Brain Neoplasms / Q000098:blood supply / Q000201:enzymology / Q000473:pathology*; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008264:Macrophages / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000473:pathology*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2