Expression of vascular endothelial growth factor receptors on tumor cells in head and neck squamous cell carcinoma.
BACKGROUND
Angiogenesis is essential for the growth of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Angiogenesis is regulated by angiogenic factors such as vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) 1, 2, and 3 known to be located on vascular endothelial cells (VECs). We hypothesize that VEGFRs are also expressed on HNSCC tumor cells in vitro and in vivo and likely control tumor function in vivo.


METHODS
Immunohistochemical analysis for VEGFR-1 (n = 13), VEGFR-2 (n = 21), and VEGFR-3 (n = 16) was performed on human HNSCC tumor samples. Specimens were analyzed for receptor expression and staining intensity. A cultured oral SCC cell line (SCC-25) and a pharyngeal SCC cell line (FADU) were also studied for receptor expression.


RESULTS
The HNSCC tumor cells expressed VEGFR-1, VEGFR-2, and VEGFR-3 in all specimens evaluated. Staining for all 3 receptors was also found on tumor-associated macrophages and fibroblasts, except that VEGFR-2 was not present on fibroblasts. Staining intensity for VEGFR-1 and VEGFR-2 was significantly higher in tumor cells and macrophages than in VECs stained for the same receptor. Both cultured HNSCC cell lines demonstrated expression of all 3 receptors.


CONCLUSIONS
This represents the first report of all 3 VEGFRs being expressed by HNSCC cells. These findings indicate that VEGF may be an autocrine regulator of tumor cell activity in addition to its known angiogenic effects on VECs. The presence of VEGFRs on tumor-associated macrophages and fibroblasts contributes to the complexity of the VEGF/VEGFR system in human cancer.
Lalla
Rajesh V
RV
Division of Oral Medicine, Department of Oral Diagnosis, University of Connecticut Health Center, Farmington, Conn., USA.
Boisoneau
David S
DS
Spiro
Jeffrey D
JD
Kreutzer
Donald L
DL
D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008264:Macrophages / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism; D014407:Tumor Cells, Cultured; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000096:biosynthesis*
D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3