J Korean Assoc Maxillofac Plast Reconstr Surg.  2013 Jan;35(1):1-12.

Effect of Lymphangiogenic Factors on Survival in a Murine Model of Oral Squamous Cell Carcinoma

• Park YW
• Cho JW

Abstract

PURPOSE
Vascular endothelial growth factor (VEGF)-C and its tyrosine kinase receptor, VEGF receptor (VEGFR)-3 are recently known to have lymphangiogenic activities in various tumor types. In this study, we determined whether the expression of lymphangiogenic factors correlate with nodal metastasis or survival in a nude mouse model of oral squamous cell carcinoma (OSCC).
METHODS
Three OSCC cells (KB, SCC4, SCC9) were xenografted into the right mandibular gland of athymic nude mice. The mice were followed for tumor development and growth, and the mice were sacrificed when they had lost more than 20% of their initial body weight, or the diameter of the induced tumor exceeds 20 mm. After necropsy, the murine tumors were examined histologically and radiologically (micro-positron emission tomography computed tomography) for regional or distant metastasis. We performed immunohistochemical assays with anti-VEGF-C, VEGFR-3, CD105, and D2-40 antibodies. Immunofluorescence double staining for LYVE-1/CD31 was also performed. To quantify the VEGF-C and VEGFR-3 level in the cancer tissue, Western blotting was performed. Finally, we determined the correlation between the degree of expression of VEGF-C/VEGFR-3 and the mean survival time.
RESULTS
OSCC tumor cells into the mandibular gland of the nude mice successfully resulted in the formation of recapitulating orthotopic tumor. Tumor cells of the induced tumor did not express VEGF-C. VEGF-C/VEGFR-3 expression was mainly distributed in the endothelial cells of the stromal area. There were no correlation between the degree of expression of VEGF-C/VEGFR-3 and the mean survival time of mice injected with different OSCC cell lines.
CONCLUSION
An recapitulating orthotopic model of OSCC in nude mice was established, which copies the cervical nodal metastasis of human OSCC. Overexpression of lymphangiogenic factors seems to have no effect on survival of hosts in this in vivo experiment.

Keyword

Oral squamous cell carcinoma; Recapitulating orthotopic nude mouse model; Lymphangiogenic factor; Survival study

MeSH Terms

Animals
Antibodies
Blotting, Western
Body Weight
Carcinoma, Squamous Cell
Coat Protein Complex I
Endothelial Cells
Fluorescent Antibody Technique
Growth and Development
Humans
Mice
Mice, Nude
Neoplasm Metastasis
Protein-Tyrosine Kinases
Receptors, Vascular Endothelial Growth Factor
Survival Rate
Transplantation, Heterologous
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor C
Vascular Endothelial Growth Factor Receptor-3
Antibodies
Coat Protein Complex I
Protein-Tyrosine Kinases
Receptors, Vascular Endothelial Growth Factor
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor C
Vascular Endothelial Growth Factor Receptor-3