http://www.cnr.it/ontology/cnr/individuo/prodotto/ID63043
A placental growth factor 2 variant acts as dominant negative of vascular endothelial growth factor A by heterodimerization mechanism. (Articolo in rivista)
- Type
- Label
- A placental growth factor 2 variant acts as dominant negative of vascular endothelial growth factor A by heterodimerization mechanism. (Articolo in rivista) (literal)
- Anno
- 2011-01-01T00:00:00+01:00 (literal)
- Alternative label
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Tarallo V, Tudisco L and De Falco S. (literal)
- Pagina inizio
- Pagina fine
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3180054/ (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
- Rivista
- Note
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
- Angiogenesis Lab, Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso', Consiglio Nazionale delle Ricerche,
Napoli, Italy (literal)
- Titolo
- A placental growth factor 2 variant acts as dominant negative of vascular endothelial growth factor A by heterodimerization mechanism. (literal)
- Abstract
- Angiogenesis is one of the crucial events for cancer development and growth and vascular endothelial
growth factor (VEGF) family plays an essential role in this biological phenomenon. The members of VEGF family
mainly involved in angiogenesis are VEGF-A, VEGF-B and placental growth factor (PlGF), which exert their activity
through the binding and activation of two VEGF receptors, VEGFR-1 and VEGFR-2. Human VEGF-A and PlGF are expressed
in different isoforms and have the peculiarity to form heterodimer if co-expressed in the same cell. The difference
of two main human PlGF isoforms, PlGF1 and PlGF2, consist in the exclusive ability of PlGF2 to bind heparin
and Neuropilin receptors. As previously reported for PlGF1 isoform, we have generated a PlGF2 variant named PlGF2
-DE, in which the residues D72 and E73 were substituted with alanine, that is unable to bind and activate VEGFR-1 but
is still able to heterodimerize with VEGF. Here we report that overexpression in VEGF-A producing human tumor cell
line derived from ovarian carcinoma (A2780) of PlGF2-DE variant by stable transfection, significantly reduces the
production of VEGF-A homodimer via heterodimerization, determining a strong inhibition of xenograft tumor growth
and associated neoangiogenesis, as well as significant reduction of monocyte-macrophage infiltration. Conversely,
the overexpression of PlGF2wt, also reducing the VEGF-A homodimer production comparably to PlGF2-DE variant
through the generation of VEGF-A/PlGF2 heterodimer, does not inhibit tumor growth and vessel density compared to
control, but induces increase of monocyte-macrophage infiltration. Interestingly the comparison of PlGF2wt with
PlGF1wt overexpression evidences a significant reduction of monocyte-macrophages recruitment as unique difference
among the activity of the two PlGFwt isoforms. Therefore, the 'less soluble' PlGF2 shows a limited potential in
monocyte-macrophages recruitment. In conclusion data here reported demonstrate that PlGF-DE variant acts as
'dominant negative' of VEGF-A independently from the PlGF isoform utilized, that the expression of active PlGF2
homodimer and VEGF-A/PlGF2 heterodimer is sufficient to rescue pro-angiogenic activity lost for reduction of VEGF-A
due to heterodimerization mechanism, and that PlGF2 shows lower activity into recruitment of monocyte-macrophage
cells compared to PlGF1 isoform. (literal)
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