NRP1 presented in trans to the endothelium arrests VEGFR2 endocytosis, preventing angiogenic signaling and tumor initiation.
Dev Cell
; 28(6): 633-46, 2014 Mar 31.
Article
in En
| MEDLINE
| ID: mdl-24656741
ABSTRACT
Neuropilin 1 (NRP1) modulates angiogenesis by binding vascular endothelial growth factor (VEGF) and its receptor, VEGFR2. We examined the consequences when VEGFR2 and NRP1 were expressed on the same cell (cis) or on different cells (trans). In cis, VEGF induced rapid VEGFR2/NRP1 complex formation and internalization. In trans, complex formation was delayed and phosphorylation of phospholipase Cγ (PLCγ) and extracellular regulated kinase 2 (ERK2) was prolonged, whereas ERK1 phosphorylation was reduced. Trans complex formation suppressed initiation and vascularization of NRP1-expressing mouse fibrosarcoma and melanoma. Suppression in trans required high-affinity, steady-state binding of VEGF to NRP1, which was dependent on the NRP1 C-terminal domain. Compatible with a trans effect of NRP1, quiescent vasculature in the developing retina showed continuous high NRP1 expression, whereas angiogenic sprouting occurred where NRP1 levels fluctuated between adjacent endothelial cells. Therefore, through communication in trans, NRP1 can modulate VEGFR2 signaling and suppress angiogenesis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Melanoma, Experimental
/
Endothelium, Vascular
/
Vascular Endothelial Growth Factor Receptor-2
/
Neuropilin-1
/
Endocytosis
/
Fibrosarcoma
/
Neovascularization, Pathologic
Limits:
Animals
/
Humans
Language:
En
Journal:
Dev Cell
Journal subject:
EMBRIOLOGIA
Year:
2014
Document type:
Article
Affiliation country:
Sweden
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA