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EGF Potentiation of VEGF Production Is Cell Density Dependent in H292 EGFR Wild Type NSCLC Cell Line

Non-small cell lung cancer (NSCLC) affects millions of patients each year worldwide. Existing therapies include epidermal growth factor receptor (EGFR) inhibition using small molecules or antibodies with good efficacy. Unfortunately, intrinsic and acquired resistance to EGFR therapy remains a persis...

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Detalles Bibliográficos
Autores principales: Ranayhossaini, Daniel J., Lu, Jin, Mabus, John, Gervais, Alexis, Lingham, Russell B., Fursov, Natalie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227184/
https://www.ncbi.nlm.nih.gov/pubmed/25272226
http://dx.doi.org/10.3390/ijms151017686
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author Ranayhossaini, Daniel J.
Lu, Jin
Mabus, John
Gervais, Alexis
Lingham, Russell B.
Fursov, Natalie
author_facet Ranayhossaini, Daniel J.
Lu, Jin
Mabus, John
Gervais, Alexis
Lingham, Russell B.
Fursov, Natalie
author_sort Ranayhossaini, Daniel J.
collection PubMed
description Non-small cell lung cancer (NSCLC) affects millions of patients each year worldwide. Existing therapies include epidermal growth factor receptor (EGFR) inhibition using small molecules or antibodies with good efficacy. Unfortunately, intrinsic and acquired resistance to EGFR therapy remains a persistent complication for disease treatment. A greater understanding of the role of EGFR in NSCLC etiology is crucial to improving patient outcomes. In this study, the role of EGFR in tumor angiogenesis was examined in H292 NSCLC cells under the pretense that confluent cells would exhibit a more angiogenic and growth-centered phenotype. Indeed, confluent H292 cells potentiated endothelial cell angiogenesis in co-culture models in an EGFR-dependent manner. While confluent H292 cells did not exhibit any change in EGFR protein expression, EGFR localization to the extracellular membrane was increased. EGFR membrane localization coincided with a comparable potentiation of maximal EGFR phosphorylation and was followed by a 3-fold increase in vascular endothelial growth factor A (VEGF-A) production as compared to subconfluent cells. EGFR-mediated VEGF-A production was determined to be dependent on signal transducer and activator of transcription 3 (STAT3) activation and not phosphoinositide 3-kinase (PI3K) signaling. These results identify unique cell density dependent phenotypes within a monoclonal NSCLC cell line and provide a potential mechanism of resistance to anti-EGFR therapy in metastatic NSCLC.
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spelling pubmed-42271842014-11-12 EGF Potentiation of VEGF Production Is Cell Density Dependent in H292 EGFR Wild Type NSCLC Cell Line Ranayhossaini, Daniel J. Lu, Jin Mabus, John Gervais, Alexis Lingham, Russell B. Fursov, Natalie Int J Mol Sci Article Non-small cell lung cancer (NSCLC) affects millions of patients each year worldwide. Existing therapies include epidermal growth factor receptor (EGFR) inhibition using small molecules or antibodies with good efficacy. Unfortunately, intrinsic and acquired resistance to EGFR therapy remains a persistent complication for disease treatment. A greater understanding of the role of EGFR in NSCLC etiology is crucial to improving patient outcomes. In this study, the role of EGFR in tumor angiogenesis was examined in H292 NSCLC cells under the pretense that confluent cells would exhibit a more angiogenic and growth-centered phenotype. Indeed, confluent H292 cells potentiated endothelial cell angiogenesis in co-culture models in an EGFR-dependent manner. While confluent H292 cells did not exhibit any change in EGFR protein expression, EGFR localization to the extracellular membrane was increased. EGFR membrane localization coincided with a comparable potentiation of maximal EGFR phosphorylation and was followed by a 3-fold increase in vascular endothelial growth factor A (VEGF-A) production as compared to subconfluent cells. EGFR-mediated VEGF-A production was determined to be dependent on signal transducer and activator of transcription 3 (STAT3) activation and not phosphoinositide 3-kinase (PI3K) signaling. These results identify unique cell density dependent phenotypes within a monoclonal NSCLC cell line and provide a potential mechanism of resistance to anti-EGFR therapy in metastatic NSCLC. MDPI 2014-09-30 /pmc/articles/PMC4227184/ /pubmed/25272226 http://dx.doi.org/10.3390/ijms151017686 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ranayhossaini, Daniel J.
Lu, Jin
Mabus, John
Gervais, Alexis
Lingham, Russell B.
Fursov, Natalie
EGF Potentiation of VEGF Production Is Cell Density Dependent in H292 EGFR Wild Type NSCLC Cell Line
title EGF Potentiation of VEGF Production Is Cell Density Dependent in H292 EGFR Wild Type NSCLC Cell Line
title_full EGF Potentiation of VEGF Production Is Cell Density Dependent in H292 EGFR Wild Type NSCLC Cell Line
title_fullStr EGF Potentiation of VEGF Production Is Cell Density Dependent in H292 EGFR Wild Type NSCLC Cell Line
title_full_unstemmed EGF Potentiation of VEGF Production Is Cell Density Dependent in H292 EGFR Wild Type NSCLC Cell Line
title_short EGF Potentiation of VEGF Production Is Cell Density Dependent in H292 EGFR Wild Type NSCLC Cell Line
title_sort egf potentiation of vegf production is cell density dependent in h292 egfr wild type nsclc cell line
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227184/
https://www.ncbi.nlm.nih.gov/pubmed/25272226
http://dx.doi.org/10.3390/ijms151017686
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