Expression of VEGF receptors in cocultured neuroblastoma cells

Elizabeth A. Beierle, Wei Dai, Max Langham, Edward M. Copeland, Mike K. Chen

Research output: Contribution to journalArticle

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Abstract

Background VEGF is best known for its angiogenic properties. We have found that VEGF expression is increased in neuroblastoma cells cocultured with hepatocytes. In addition, we have previously shown that neuroblastoma cells cultured with exogenous VEGF have an increase in the expression of VEGF receptors. Therefore, we hypothesized that the expression of VEGF receptors would be up-regulated in neuroblastoma cells grown in the coculture environment. Materials and methods Two neuroblastoma cell lines (IMR-32 or SK-N-DZ) are used. These cells are cultured alone and in a coculture system with hepatocytes. Message for VEGF and the VEGF receptors KDR, flt-1, flt-4, neuropilin 1 (NRP-1), and neuropilin 2 (NRP-2) are measured with RT-PCR. Flt-4, NRP-1, and NRP-2 protein expression is measured with Western blot. Results The receptors KDR and flt-1 are not detected in either cell line in either control or coculture conditions. Message for VEGF and flt-4 is significantly increased in the cocultured IMR-32 cells, while that for NRP-1 and NRP-2 is unchanged in these cells. VEGF and its receptors are unchanged in cocultured SK-N-DZ cells. Conclusions Neuroblastoma cells express specific VEGF receptors that are differentially regulated in the different cell lines. These findings suggest that the heterogeneity of neuroblastomas may limit the utility of targeting VEGF and its receptors as sole treatments for the tumor, and that successful therapies will be dependent upon the specific biology of the tumor.

Original languageEnglish (US)
Pages (from-to)56-65
Number of pages10
JournalJournal of Surgical Research
Volume119
Issue number1
DOIs
StatePublished - Jun 1 2004
Externally publishedYes

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Vascular Endothelial Growth Factor Receptor
Neuroblastoma
Neuropilin-2
Vascular Endothelial Growth Factor A
Neuropilin-1
Vascular Endothelial Growth Factor Receptor-3
Coculture Techniques
Cell Line
Hepatocytes
Cultured Cells
Vascular Endothelial Growth Factor Receptor-2
Neoplasms
Western Blotting
Polymerase Chain Reaction
Proteins

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Expression of VEGF receptors in cocultured neuroblastoma cells. / Beierle, Elizabeth A.; Dai, Wei; Langham, Max; Copeland, Edward M.; Chen, Mike K.

In: Journal of Surgical Research, Vol. 119, No. 1, 01.06.2004, p. 56-65.

Research output: Contribution to journalArticle

Beierle, Elizabeth A. ; Dai, Wei ; Langham, Max ; Copeland, Edward M. ; Chen, Mike K. / Expression of VEGF receptors in cocultured neuroblastoma cells. In: Journal of Surgical Research. 2004 ; Vol. 119, No. 1. pp. 56-65.
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N2 - Background VEGF is best known for its angiogenic properties. We have found that VEGF expression is increased in neuroblastoma cells cocultured with hepatocytes. In addition, we have previously shown that neuroblastoma cells cultured with exogenous VEGF have an increase in the expression of VEGF receptors. Therefore, we hypothesized that the expression of VEGF receptors would be up-regulated in neuroblastoma cells grown in the coculture environment. Materials and methods Two neuroblastoma cell lines (IMR-32 or SK-N-DZ) are used. These cells are cultured alone and in a coculture system with hepatocytes. Message for VEGF and the VEGF receptors KDR, flt-1, flt-4, neuropilin 1 (NRP-1), and neuropilin 2 (NRP-2) are measured with RT-PCR. Flt-4, NRP-1, and NRP-2 protein expression is measured with Western blot. Results The receptors KDR and flt-1 are not detected in either cell line in either control or coculture conditions. Message for VEGF and flt-4 is significantly increased in the cocultured IMR-32 cells, while that for NRP-1 and NRP-2 is unchanged in these cells. VEGF and its receptors are unchanged in cocultured SK-N-DZ cells. Conclusions Neuroblastoma cells express specific VEGF receptors that are differentially regulated in the different cell lines. These findings suggest that the heterogeneity of neuroblastomas may limit the utility of targeting VEGF and its receptors as sole treatments for the tumor, and that successful therapies will be dependent upon the specific biology of the tumor.

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