J Korean Assoc Maxillofac Plast Reconstr Surg.  2008 Nov;30(6):529-539.

Expressions of Metastasis-Related Factors in Orthotopic Tumor Models of Oral Squamous Cell Carcinoma

• Park YW
• Lee JW
• Kim SH

Abstract

BACKGROUND AND PURPOSE
Oral squamous cell carcinoma (OSCC) is one of the most aggressive tumors of the head and neck area. OSCC is known to preferentially metastasize via lymphatic system, and resulting cervical lymph node metastasis is the most reliable of treatment failure. But the biological mechanism of the regional nodal metastasis is not clear. So, we determined metastasis-related factors in orthotopic nude mouse models of OSCC. EXPERIMENTAL DESIGN: Two cell lines-KB and YD-10B cells, established from human oral mucosal squamous cell carcinoma, were xenografted into the tissue space of athymic murine mouth floor. The mice were followed for tumor development and growth, the murine tumors were examined histopathologically for local invasion or regional or distant metastasis. Finally, we performed immunohistochemical assays with antiepithelial growth factor (EGF), EGF receptor (EGFR), phosphorylated EGFR (pEGFR), and anti-vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-2, phosphorylated VEGFR-2/3 (pVEGFR-2/3) antibodies. We also determined the microvessel density.
RESULTS
Transplantation of human OSCC tumor cells into the mouth floor successfully resulted in the formation of orthotopic tumors. KB cell line showed significantly higher tumor proliferation and higher nodal metastatic potential than YD-10B cell line. Furthermore, immunohistochemical staining demonstrated higher expression of EGFR/pEGFR, VEGF, and pVEGFR-2/3 as well as higher microvessel density in KB murine tumors than in YD-10B murine tumors.
CONCLUSION
An orthotopic model of OSCC in athymic mice was established which copies the cervical lymph nodal metastasis of human OSCC. Our mouth floor model should facillitate the understanding of the molecular pathogenesis of cervical nodal metastasis of OSCC.

Keyword

Oral squamous cell carcinoma; Lymph node metastasis; Metastasis-related factors; Mouth floor model

MeSH Terms

Animals
Antibodies
Carcinoma, Squamous Cell
Cell Line
Coat Protein Complex I
Endothelial Growth Factors
Growth and Development
Head
Humans
KB Cells
Lymph Nodes
Lymphatic System
Mice
Mice, Nude
Microvessels
Mouth Floor
Neck
Neoplasm Metastasis
Receptor, Epidermal Growth Factor
Receptors, Vascular Endothelial Growth Factor
Transplantation, Heterologous
Transplants
Treatment Failure
Vascular Endothelial Growth Factor A
Antibodies
Coat Protein Complex I
Endothelial Growth Factors
Receptor, Epidermal Growth Factor
Receptors, Vascular Endothelial Growth Factor
Vascular Endothelial Growth Factor A