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Modulation of endothelial cell network formation in vitro by molecular signaling of head and neck squamous cell carcinoma (HNSCC) exposed to cetuximab
- Source :
- Microvascular research. 83(2)
- Publication Year :
- 2011
-
Abstract
- 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.
- Subjects :
- Vascular Endothelial Growth Factor A
Pathology
medicine.medical_specialty
Angiogenesis
Cell Survival
Cetuximab
Neovascularization, Physiologic
Angiogenesis Inhibitors
Biology
Antibodies, Monoclonal, Humanized
Biochemistry
Cell surface receptor
Cell Line, Tumor
Proto-Oncogene Proteins
Paracrine Communication
medicine
Human Umbilical Vein Endothelial Cells
Humans
Secretion
Angiogenic Proteins
Receptor, Notch4
neoplasms
Dose-Response Relationship, Drug
Receptors, Notch
Antibodies, Monoclonal
Cell Biology
medicine.disease
Head and neck squamous-cell carcinoma
Vascular Endothelial Growth Factor Receptor-2
Tongue Neoplasms
Endothelial stem cell
ErbB Receptors
Platelet Endothelial Cell Adhesion Molecule-1
stomatognathic diseases
Culture Media, Conditioned
Monoclonal
Cancer research
Carcinoma, Squamous Cell
Cardiology and Cardiovascular Medicine
Intracellular
medicine.drug
Subjects
Details
- ISSN :
- 10959319
- Volume :
- 83
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Microvascular research
- Accession number :
- edsair.doi.dedup.....3c72b79525587a5b6c0cbda14eccb716