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

International Journal of Molecular Sciences

Daniel J. Ranayhossaini²  Jin Lu²  John Mabus¹  Alexis Gervais²  Russell B. Lingham²  Natalie Fursov² 

[1] Cardiovascular & Metabolic Disease, Janssen Research and Development, Welsh & McKean Roads, Spring House, PA 19477, USA; E-Mail:;Biologics Research, Janssen Research and Development, Welsh & McKean Roads, Spring House, PA 19477, USA; E-Mails:

关键词: non-small cell lung cancer;    vascular endothelial growth factor;    epidermal growth factor receptor;    cell density;   

DOI  :  10.3390/ijms151017686

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.