作者: Jane S. Wey , Fan Fan , Michael J. Gray , Todd W. Bauer , Marya F. McCarty
DOI: 10.1002/CNCR.21145
关键词:
摘要: BACKGROUND Vascular endothelial growth factor receptor-1 (VEGFR-1) is one of three receptor tyrosine kinases for VEGF, a key regulator angiogenesis in cancer. Although VEGFRs initially were believed to be expressed exclusively on cells (ECs), recent studies have demonstrated the presence VEGFR-1 non-EC types. The authors hypothesized that present and functional pancreatic carcinoma cells, contributing malignant phenotype. METHODS The assessed expression its ligands 11 cell lines by reverse-transcriptase–polymerase chain reaction, enzyme-linked immunosorbent assay, and/or Western blot analysis. function was evaluated treating two representative with VEGF-B, selective ligand VEGFR-1, specific anti-VEGFR-1 antibody assessing effects signaling, migration, invasion, proliferation. RESULTS All mRNA protein, as well VEGF-A VEGF-B. Two (L3.6 Panc-1) exhibited VEGF-B-induced mitogen-activated protein kinase signaling. A neutralizing abrogated confirming effect mediated through VEGFR-1. stimulation or VEGF-B found promote migration both lines. Panc-1 also enhanced Matrigel invasion after stimulation. VEGFR-1-dependent blocked antibody. activation did not appear enhance proliferation. CONCLUSIONS VEGFR-1 appears ubiquitously lines, which it induces signaling promotes invasion. Overexpression VEGF tumors may activate tumor bearing via an autocrine pathway. Agents targeting receptors dual inhibitory suppressing function. Cancer 2005. © 2005 American Society.