Reference : Vascular endothelial growth factor expression correlates with matrix metalloproteinas...
Scientific journals : Article
Human health sciences : Oncology
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/23925
Vascular endothelial growth factor expression correlates with matrix metalloproteinases MT1-MMP, MMP-2 and MMP-9 in human glioblastomas.
English
Munaut, Carine mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Noël, Agnès mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
Hougrand, Olivier mailto [Centre Hospitalier Universitaire de Liège - CHU > > Anatomie pathologique >]
Foidart, Jean-Michel mailto [Université de Liège - ULg > Département des sciences cliniques > Gynécologie - Obstétrique - Labo de biologie des tumeurs et du développement >]
Boniver, Jacques mailto [Centre Hospitalier Universitaire de Liège - CHU > > Anatomie pathologique >]
Deprez, Manuel [Université de Liège - ULg > Département des sciences cliniques > Neuropathologie >]
2003
International Journal of Cancer = Journal International du Cancer
Wiley Liss, Inc.
106
6
848-55
Yes (verified by ORBi)
International
0020-7136
1097-0215
New York
NY
[en] Adult ; Aged ; Brain Neoplasms/genetics/metabolism/pathology ; DNA Primers ; Female ; Gelatin/metabolism ; Glioblastoma/genetics/metabolism/pathology ; Humans ; Immunoenzyme Techniques ; Juniperus ; Male ; Matrix Metalloproteinase 2/genetics/metabolism ; Matrix Metalloproteinase 9/genetics/metabolism ; Matrix Metalloproteinases, Membrane-Associated ; Metalloendopeptidases/genetics/metabolism ; Middle Aged ; RNA, Messenger/genetics/metabolism ; Receptors, Vascular Endothelial Growth Factor/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tissue Inhibitor of Metalloproteinase-2/genetics/metabolism ; Vascular Endothelial Growth Factor A/genetics/metabolism
[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.
http://hdl.handle.net/2268/23925
also: http://hdl.handle.net/2268/60891 ; http://hdl.handle.net/2268/19528
10.1002/ijc.11313
Copyright 2003 Wiley-Liss, Inc.

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