[en] Vascular endothelial growth factor (VEGF) is the major endothelial mitogen in central nervous system neoplasms and it is expressed in 64-95% of glioblastomas (GBMs). Tumour cells are the main source of VEGF in GBMs whereas VEGF receptors (VEGFR-1, its soluble form sVEGFR-1, VEGFR-2 and neuropilin-1) are expressed predominantly by endothelial cells. Infiltrating tumour cells and newly-formed capillaries progress through the extracellular matrix by local proteolysis involving matrix metalloproteinases (MMPs). Recent studies have shown that VEGF expression and bioavailability can be modulated by MMPs. We reported previously that the expression of MT1-MMP in human breast cancer cells was associated with an enhanced VEGF expression. We used quantitative RT-PCR, Western blot, gelatin zymography and immunohistochemistry to study the expression of VEGF, VEGFR-1, VEGFR-2, sVEGFR-1, neuropilin-1, MT1-MMP, MMP-2, MMP-9 and TIMP-2 in 20 human GBMs and 5 normal brains. The expression of these MMPs was markedly increased in most GBMs with excellent correlation between mRNA and protein levels; activated forms of MMP-2 and MMP-9 were present in 8/18 and 7/18 of GBMs. A majority of GBMs (17/20) also expressed high levels of VEGF, as previously reported, with strong correlation between VEGF and MT1-MMP gene expression levels, and double immunostaining showed that VEGF and MT1-MMP peptides co-localize in tumour and endothelial cells. Our results suggest that the interplay between metalloproteinases and VEGF previously described in experimental tumours may also be operative in human GBMs. Because of its dual ability to activate MMP-2 and to up-regulate VEGF, MT1-MMP might be of central importance in the growth of GBMs and represent an interesting target for anti-cancer treatments.
Munaut, Carine ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Hougrand, Olivier ; Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique
Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique - Labo de biologie des tumeurs et du développement
Boniver, Jacques ; Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique
Deprez, Manuel ; Université de Liège - ULiège > Département des sciences cliniques > Neuropathologie
Language :
English
Title :
Vascular endothelial growth factor expression correlates with matrix metalloproteinases MT1-MMP, MMP-2 and MMP-9 in human glioblastomas.
Publication date :
2003
Journal title :
International Journal of Cancer
ISSN :
0020-7136
eISSN :
1097-0215
Publisher :
Wiley Liss, Inc., New York, United States - New York
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