The RON tyrosine kinase receptor regulates vascular endothelial growth factor production in pancreatic cancer cells.
Pancreas
; 39(3): 301-7, 2010 Apr.
Article
en En
| MEDLINE
| ID: mdl-20358644
ABSTRACT
OBJECTIVES:
The RON receptor mediates tumorigenic phenotypes in pancreatic cancer (PC), but no investigations currently have implicated RON signaling as a regulator of angiogenesis in PC. Angiogenesis is vital to oncogenesis, and vascular endothelial growth factor (VEGF) is the most well-characterized angiogenic protein. This study sought to determine the effect of RON stimulation on in vitro angiogenesis and VEGF production in PC cell lines.METHODS:
Vascular endothelial growth factor levels from conditioned media of hepatocyte growth factor-like protein-stimulated BxPC-3 and FG cells were quantitated via enzyme-linked immunosorbent assay and likewise interrogated in the presence and absence of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase/AKT inhibitors. To determine in vitro angiogenesis, human microvascular endothelial cells were subsequently exposed to the same conditioned media to assay for microtubule formation.RESULTS:
RON signaling resulted in a 52% and 34% increase in VEGF levels in BxPC-3 and FG cells, respectively. Vascular endothelial growth factor secretion was inhibited with MAPK or phosphatidylinositol-3-kinase blockade in BxPC-3 cells, but only MAPK inhibition resulted in decreased VEGF production in FG cells. BxPC-3 conditioned media induced tubule formation in human microvascular endothelial cells, which was abrogated by RON inhibition.CONCLUSIONS:
RON signaling results in MAPK-mediated VEGF secretion by PC cells and promotion of microtubule formation. These findings suggest another mechanism by which RON signaling may promote PC progression.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Pancreáticas
/
Proteínas Tirosina Quinasas Receptoras
/
Carcinoma Ductal Pancreático
/
Factor A de Crecimiento Endotelial Vascular
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Pancreas
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos