The RON tyrosine kinase receptor regulates vascular endothelial growth factor production in pancreatic cancer cells.

The RON tyrosine kinase receptor regulates vascular endothelial growth factor production in pancreatic cancer cells.
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DOI:
10.1097/mpa.0b013e3181bb9f73
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发表时间:
2010-04
期刊:
影响因子:
2.9
通讯作者:
Lowy AM
Lowy AM
中科院分区:
医学4区
文献类型:
--
作者:
Thomas RM;Jaquish DV;French RP;Lowy AM

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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. VEGF levels from conditioned media of HGFL-stimulated BxPC-3 and FG cells were quantitated via ELISA and likewise interrogated in the presence and absence of MAPK and PI3K/AKT inhibitors. To determine in vitro angiogenesis, HMVEC cells were subsequently exposed to the same conditioned media to assay for microtubule formation. RON signaling resulted in a 52% and 34% increase in VEGF levels in BxPC-3 and FG cells, respectively. VEGF secretion was inhibited with MAPK or PI3K 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 HMVEC cells, which was abrogated by RON inhibition. 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.
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