J Korean Assoc Maxillofac Plast Reconstr Surg.  2011 Jan;33(1):1-9.

Inhibition of Lymphatic Endothelial Growth Factor Receptor in a Murine Model of Oral Squamous Cell Carcinoma

• Kye JY
• Park YW

Abstract

PURPOSE
Tumor associated angiogenesis and/or lymphangiogenesis are known to be linked by VEGFR signaling pathways. These processes are regulated by several growth factors including VEGFR-2, VEGFR-3. E7080 is an orally active inhibitor of multiple tyrosine kinases including VEGFR-2, 3. Therefore, it was proposed that E7080 may inhibit angiogenesis and lymphangiogenesis. The aim of this study was to determine the effect of E7080 in a nude mouse model of OSCC.
METHODS
KB cells were xenografted into the submucosal tissue of the mouth floor of athymic mice. Seven days after the xenograft, the mice were randomized into 2 groups. E7080 were administered orally to the experimental group once per day. The mice were sacrificed 3 weeks after the treatment. The tumors were examined histopathologically. Immunohistochemical assays with anti- VEGF-C, VEGFR-2, VEGFR-3, phosphorylated VEGFR-2/3 (pVEGFR-2/3), and D2-40 antibodies were then performed.
RESULTS
The transplantation of human OSCC tumor cells into the mouth floor resulted in the formation of orthotopic tumors. The experimental (E7080 treatment) group showed a slowly increased tumor volume. Moreover, immunohistochemical staining demonstrated higher levels of VEGF-C, VEGFR-2, VEGFR-3, pVEGFR-2/3 and D2-40 expression in the control group than in the experimental group.
CONCLUSION
These results suggest that E7080 may provide therapeutic benefits in OSCC.

Keyword

OSCC; Angiogenesis; Lymphangiogenesis; VEGFR; E7080

MeSH Terms

Animals
Antibodies
Carcinoma, Squamous Cell
Endothelial Growth Factors
Humans
Intercellular Signaling Peptides and Proteins
KB Cells
Lymphangiogenesis
Mice
Mice, Nude
Mouth Floor
Phosphotransferases
Receptors, Vascular Endothelial Growth Factor
Transplantation, Heterologous
Transplants
Tumor Burden
Tyrosine
Vascular Endothelial Growth Factor C
Vascular Endothelial Growth Factor Receptor-2
Vascular Endothelial Growth Factor Receptor-3
Antibodies
Endothelial Growth Factors
Intercellular Signaling Peptides and Proteins
Phosphotransferases
Receptors, Vascular Endothelial Growth Factor
Tyrosine
Vascular Endothelial Growth Factor C
Vascular Endothelial Growth Factor Receptor-2
Vascular Endothelial Growth Factor Receptor-3