VEGF receptors are differentially expressed by neuroblastoma cells in culture.

Vascular endothelial growth factor (VEGF) is best known for its angiogenic properties, but its mitogenic capacity may be more important for tumorigenesis. The ability of VEGF to induce specific biologic activities may be dependent on the amount and type of VEGF receptors present. The authors hypothesize that neuroblastoma cells express specific VEGF receptors and that their expression may be altered when the cells are exposed to differing cytokines and culture environments. Four groups of human neuroblastoma cells (IMR-32) are studied. (1) Control cells: cultured in standard media. (2) VEGF cells: VEGF added to the media. (3) Tumor necrosis factor alpha (TNF-alpha) cells: TNF-alpha added to the media. (4) Serum starved cells: cultured in serum-depleted media. Reverse transcriptase polymerase chain reaction (RT-PCR) is utilized to measure the VEGF receptors flt-1, KDR/flk-1, flt-4, neuropilin 1 (NRP-1), and neuropilin 2 (NRP-2). Flt-1 and KDR are not detected in any groups. Flt-4, NRP-1, and NRP-2 are present in the IMR-32 cells, and their expression is significantly increased by the administration of VEGF. Neuroblastoma cells cultured with TNF-alpha or in serum-depleted media have a significant decrease in the expression of these receptors. The authors show that neuroblastoma cells express specific VEGF receptors that may be altered by mitogenic or apoptotic stimuli. Specifically targeting VEGF and its receptors may be another therapeutic strategy for the treatment of neuroblastoma.

Beierle EA ，Dai W ，Langham MR Jr ，Copeland EM 3rd ，Chen MK ... -  《-》

Expression of VEGF receptors in cocultured neuroblastoma cells.

Beierle EA ，Dai W ，Langham MR Jr ，Copeland EM 3rd ，Chen MK ... -  《JOURNAL OF SURGICAL RESEARCH》

Expression and regulation of vascular endothelial growth factor ligands and receptors during menstruation and post-menstrual repair of human endometrium.

Punyadeera C ，Thijssen VL ，Tchaikovski S ，Kamps R ，Delvoux B ，Dunselman GA ，de Goeij AF ，Griffioen AW ，Groothuis PG ... -  《MOLECULAR HUMAN REPRODUCTION》

Expression of the vascular endothelial growth factor receptor neuropilin-1 in the human endometrium.

Hess AP ，Schanz A ，Baston-Buest DM ，Hirchenhain J ，Stoff-Khalili MA ，Bielfeld P ，Kruessel JS ... -  《-》

Expression and regulation of the novel vascular endothelial growth factor receptor neuropilin-1 by epidermal growth factor in human pancreatic carcinoma.

It was recently shown that neuropilin-1 (NRP-1), which was described originally as a receptor for the semaphorins/collapsins (ligands involved in neuronal guidance), is a coreceptor for vascular endothelial growth factor (VEGF) and increases the affinity of specific isoforms of VEGF to its receptor, VEGF-R2. The authors investigated the expression and regulation of NRP-1 in human pancreatic adenocarcinoma specimens and cell lines. Immunohistochemical analysis revealed that NRP-1 was expressed in 12 of 12 human pancreatic adenocarcinoma specimens but was absent in nonmalignant pancreatic tissue. Northern blot analysis revealed NRP-1 mRNA expression in 8 of 11 human pancreatic adenocarcinoma cell lines. NRP-1 mRNA expression was increased by epidermal growth factor (EGF) but not by tumor necrosis factor alpha in several of the human pancreatic adenocarcinoma cell lines studied. Treating human Panc-48 adenocarcinoma cells with EGF activated Akt and Erk but not P-38. Blockade of the phosphatidylinositol-3 kinase (PI-3K)/Akt, mitogen-activated protein kinase (MAPK)/Erk, or P-38 pathways abrogated EGF-induced NRP-1 expression. Finally, EGF receptor blockade in vivo led to a decrease in NRP-1 expression in an orthotopic model of human pancreatic carcinoma. NRP-1 is expressed in most human pancreatic adenocarcinomas and cell lines but not in nonmalignant pancreatic tissue. EGF regulates NRP-1 expression through the PI-3K/Akt and MAPK/Erk signaling pathways, and blockade of the EGF receptor is associated with decreased expression of NRP-1 in vivo. NRP-1 may act as a coreceptor for VEGF in pancreatic carcinoma, as it does in other tumor systems, thereby enhancing angiogenesis and the effect of VEGF on the growth of pancreatic adenocarcinoma.

Parikh AA ，Liu WB ，Fan F ，Stoeltzing O ，Reinmuth N ，Bruns CJ ，Bucana CD ，Evans DB ，Ellis LM ... -  《CANCER》