Modulation of endothelial cell network formation in vitro by molecular signaling of head and neck squamous cell carcinoma (HNSCC) exposed to cetuximab.
Fiche publication
Date publication
mars 2012
Journal
Microvascular research
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FAIVRE Béatrice, Pr MERLIN Jean-Louis, Pr BOURA Cédric
Tous les auteurs :
Jouan-Hureaux V, Boura C, Merlin JL, Faivre B
Lien Pubmed
Résumé
Overexpression of EGFR plays a key-role in head and neck squamous cell carcinoma (HNSCC) and justifies the extensive use of cetuximab, a monoclonal anti-EGFR antibody, as well as EGFR-tyrosine kinase inhibitors (EGFR-TKI), which have been reported to inhibit tumor cell growth and the secretion of pro-angiogenic factors by tumor cells, such as VEGF and IL-8. Moreover, vessel normalization in tumors, suggesting a more complex mediation of endothelial cell growth control has also been observed in vivo. The present study was designed to investigate the angiogenic consequences of exposure of HNSCC tumor cell lines to cetuximab and intercellular signaling between tumor and endothelial cells by secretion of pro- and anti-angiogenic mediators in the conditioned media (CM). The results achieved showed that cetuximab decreased the secretion of VEGF by HNSCC cells and that exposure of human umbilical vein endothelial cells (HUVEC) to CM from HNSCC cells exposed to cetuximab induced an increase in endothelial cell network formation. Angiogenesis proteome profiling showed that cetuximab induced a complex alteration of the secretion of pro- and anti-angiogenic factors by HNSCC cells without enabling to identify a unique molecular marker. Expression of endothelial membrane receptors (VEGFR-2, EGFR, PECAM-1 and Notch-4) was investigated and only EGFR expression was found influenced when HUVEC were exposed to CM from cetuximab-exposed HNSCC cells. These results showed that the decrease in the secretion of pro-angiogenic agents like VEGF by HNSCC cells exposed to cetuximab could not be sufficient to justify its anti-angiogenic activity in vitro.
Mots clés
Angiogenesis Inhibitors, pharmacology, Angiogenic Proteins, metabolism, Antibodies, Monoclonal, pharmacology, Antibodies, Monoclonal, Humanized, Antigens, CD31, metabolism, Carcinoma, Squamous Cell, metabolism, Cell Line, Tumor, Cell Survival, drug effects, Cetuximab, Culture Media, Conditioned, metabolism, Dose-Response Relationship, Drug, Human Umbilical Vein Endothelial Cells, metabolism, Humans, Neovascularization, Physiologic, drug effects, Paracrine Communication, drug effects, Proto-Oncogene Proteins, metabolism, Receptor, Epidermal Growth Factor, antagonists & inhibitors, Receptors, Notch, metabolism, Tongue Neoplasms, metabolism, Vascular Endothelial Growth Factor A, metabolism, Vascular Endothelial Growth Factor Receptor-2, metabolism
Référence
Microvasc. Res.. 2012 Mar;83(2):131-7