Upregulation of vascular endothelial growth factor receptors is associated with advanced neuroblastoma

Fakhari, Mitra; Pullirsch, Dieter; Paya, Kurosh; Abraham, Dietmar; Hofbauer, Roland; Aharinejad, Seyedhossein

doi:10.1053/jpsu.2002.31614

Cited by 44 publications

(33 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…VEGFR-1 is elevated in advanced-stage neuroblastoma (Fakhari et al, 2002). We treated SK-N-AS cells with the VEGFR-1-specific ligand, VEGF-B, and observed increased migration.…”

Section: Discussionmentioning

confidence: 95%

“…Although sunitinib and sorafenib were designed to primarily target the tumor vasculature, there is evidence that neuroblastoma cells themselves may express VEGFR-1, PDGFR and RET. Neuroblastoma tumors have been shown to express PDGFR and c-Kit (Beppu et al, 2004), and VEGFR-1 is elevated in advanced-stage neuroblastoma (Cohen et al, 1994;Meister et al, 1999;Langer et al, 2000;Fakhari et al, 2002). We and others have shown RET overexpression on neuroblastoma cells (Nakamura et al, 1994;Hishiki et al, 1998;Beaudry et al, 2008), and activation of RET by its ligand, glial-derived neurotrophic factor (GDNF), initiates cell proliferation, migration and survival (Richardson et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Multiple receptor tyrosine kinases regulate HIF-1α and HIF-2α in normoxia and hypoxia in neuroblastoma: implications for antiangiogenic mechanisms of multikinase inhibitors

et al. 2010

View full text Add to dashboard Cite

Novel treatment approaches are needed for children with advanced neuroblastoma. Studies with neuroblastoma cells have indicated the presence of a hypoxiadriven vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-1 autocrine loop modulating hypoxiainducible factor-1alpha (HIF-1a). Whether other receptor tyrosine kinases (RTKs) are capable of modulating HIF1a levels and whether RTKs can regulate HIF-2a as well is largely unknown. We evaluated neuroblastoma cell lines for expression of various RTKs. Although cell lines were heterogeneous in the expression of VEGFR-1, -3, c-Kit and RET, most cells expressed PDGFR-a and -b. Ligandinduced activation of multiple RTKs upregulated HIF-1a levels, whereas activation of VEGFR-1 alone upregulated HIF-2a. Multitargeted tyrosine kinase inhibitor sunitinib reduced hypoxia-induced rises in HIF-1a and HIF-2a through mechanisms involving effects on both mRNA levels and protein stability. In addition, sunitinib and sorafenib had direct effects on tumor cell viability in vitro. In a neuroblastoma xenograft model, tumor growth inhibition by sunitinib was associated with inhibition of angiogenesis and reduced HIF-1a levels. These findings show that multiple RTKs may regulate the HIF axis in normoxia and hypoxia and suggest that multikinase inhibitors may exert antiangiogenic effects not only by direct effects on endothelial cells, but also by blocking compensatory hypoxia-and ligand-induced changes in HIF-1a and HIF-2a.

show abstract

“…VEGFR-1 is elevated in advanced-stage neuroblastoma (Fakhari et al, 2002). We treated SK-N-AS cells with the VEGFR-1-specific ligand, VEGF-B, and observed increased migration.…”

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Multiple receptor tyrosine kinases regulate HIF-1α and HIF-2α in normoxia and hypoxia in neuroblastoma: implications for antiangiogenic mechanisms of multikinase inhibitors

et al. 2010

View full text Add to dashboard Cite

show abstract

“…It has also been envisaged the possibility that VEGF could take part to neuroblastoma progression by directly regulating neuroblastoma cell growth (51). Interestingly, in neuroblastoma tumors, VEGF, as well as VEGF-R2, expression is associated with poor prognosis (34,52). Here, we observed that the administration of vinblastine and rapamycin in combination produced a statistically significant decrease in the secretion of VEGF molecule, as well as VEGF-R2 expression, improving the effects obtained by either drug used as monotherapy.…”

Section: Discussionmentioning

confidence: 99%

Combined Therapeutic Effects of Vinblastine and Rapamycin on Human Neuroblastoma Growth, Apoptosis, and Angiogenesis

Marimpietri¹,

Brignole²,

Nico

et al. 2007

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Vinblastine and rapamycin displayed synergistic inhibition of human neuroblastomarelated angiogenesis. Here, we studied the antitumor activity of vinblastine and rapamycin against human neuroblastoma. Experimental Design: Cell proliferation, cell cycle progression, and apoptosis were evaluated by measuring 3 H-thymidine incorporation, bromodeoxyuridine uptake, and phosphatidylserine exposure, respectively. The in vivo sensitivity of neuroblastoma cells to vinblastine and rapamycin was determined in orthotopic neuroblastoma-engrafted mice. Angiogenesis was assessed by the chick embryo chorioallantoic membrane assay. Results: Each compound alone was able to induce a dose-dependent significant inhibition of cell proliferation, with a dramatically enhanced antiproliferative effect for the drugs used in combination. A marked G 2 -M cell cycle arrest with a nearly complete depletion of S phase was associated. The combined treatment triggered an increased apoptosis compared with either drug tested alone. A significant inhibition of tumor growth and microvessel area was obtained in neuroblastoma-bearing mice when treated with vinblastine or rapamycin alone, and a more dramatic effect with the combined treatment, compared with control mice. The therapeutic effectiveness, expressed as increased life span, was statistically improved by the combined therapy, compared with mice treated with either drug tested separately. Histologic evaluation of primary tumors showed that the combined treatment inhibited proliferation and angiogenesis and induced apoptosis. Combined treatment of neuroblastoma cells and neuroblastoma-bearing mice with vinblastine and rapamycin induced the down-modulation of both vascular endothelial growth factor production and vascular endothelial growth factor receptor 2 expression. In the chorioallantoic membrane assay, angiogenesis induced by humanneuroblastoma biopsy specimens was significantly inhibitedby vinblastine and rapamycin. Conclusions: These results may be relevant to design new therapeutic strategies against neuroblastoma.

show abstract

“…Neuroblastoma cell lines and primary tumors have been shown to express varying levels of these growth factors and their cognate receptors [6][7][8][9][10][11][12][13][14][15], and increased expression of many of these growth factors is associated with advanced stage high-risk neuroblastoma tumors and poor overall patient outcomes [9,15,16].…”

Section: Introductionmentioning

confidence: 99%

Sensitivity of neuroblastoma to the novel kinase inhibitor cabozantinib is mediated by ERK inhibition

Zhang

Scorsone

Woodfield

et al. 2015

Cancer Chemother Pharmacol

View full text Add to dashboard Cite

Treatment of neuroblastoma tumor cells with cabozantinib inhibits RET and ERK phosphorylation and is effective against neuroblastoma tumor cell lines alone and in combination with 13-cis-retinoic acid, topotecan, and temozolomide. Cabozantinib treatment is also effective in reducing tumor growth in vivo. Cabozantinib therefore represents a novel therapeutic agent for neuroblastoma, and further preclinical and clinical studies are warranted.

show abstract

Upregulation of vascular endothelial growth factor receptors is associated with advanced neuroblastoma

Cited by 44 publications

References 18 publications

Multiple receptor tyrosine kinases regulate HIF-1α and HIF-2α in normoxia and hypoxia in neuroblastoma: implications for antiangiogenic mechanisms of multikinase inhibitors

Multiple receptor tyrosine kinases regulate HIF-1α and HIF-2α in normoxia and hypoxia in neuroblastoma: implications for antiangiogenic mechanisms of multikinase inhibitors

Combined Therapeutic Effects of Vinblastine and Rapamycin on Human Neuroblastoma Growth, Apoptosis, and Angiogenesis

Sensitivity of neuroblastoma to the novel kinase inhibitor cabozantinib is mediated by ERK inhibition

Contact Info

Product

Resources

About