J Korean Assoc Maxillofac Plast Reconstr Surg.  2007 Nov;29(6):499-508.

Expressions of vascular metastasis related factors in murine orthotopic tumor models of salivary glands

• Jang JH
• Kwon KJ
• Park YW

Abstract

BACKGROUND AND PURPOSE: Some subtypes of malignant salivary gland tumors such as adenoid cystic carcinoma (ACC) frequently result in distant metastasis of vascular origin, which are main causes of treatment failure. The reasons for the affinity for vascular metastatic potential are unclear. Therefore, molecular characteristics that influence the dissemination of metastatic tumor cells are important for the design of more effective treatment of salivary ACC. Tumor angiogenesis has been known to be essential for the distant metastasis of malignant cells. So, we determined expressions of vascular metastasis related factors in orthotopic (parotid) murine models of parotid ACC and compared with those in ectopic (subcutis) tumors of athymic mice. EXPERIMENTAL DESIGN: Using specimens from murine parotid (orthotopic, experimental group) and subcutaneous (ectopic, control group) tumors, which have developed via transplantation of tumor cells, originated from human parotid ACC, we performed immunohistochemical assays with anti-vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF, FGF2), matrix metalloproteinase (MMP)-9, and interleukin (IL)-8 antibodies. We also performed immunohistochemical assays with VEGF receptor (VEGFR)-1, VEGFR-2, VEGFR-3, and phosphorylated VEGFR-2.
RESULTS
Transplantation of human ACC tumor cell (5x10(5)) into the parotid and subcutis successfully resulted in orthotopic (parotid) and ectopic (subcutaneous) tumors in athymic mice. Immunohistochemical staining demonstrated higher expression of major angiogenic factors (VEGF, bFGF, MMP-9) in the orthotopic tumors than in ectopic tumors (P < 0.05). But the expression level of angiogenic receptors were same in orthotopic and ectopic tumors of parotid ACC.
CONCLUSION
VEGF, bFGF, and MMP-9 could be a good candidates for antiangiogenic therapy for the contol of vascular metastatic lesions of salivary ACC.

Keyword

Adenoid cystic carcinoma; Orthotopic murine model; Vascular metastasis related factors

MeSH Terms

Angiogenesis Inducing Agents
Animals
Antibodies
Carcinoma, Adenoid Cystic
Endothelial Growth Factors
Fibroblast Growth Factor 2
Humans
Interleukins
Mice
Mice, Nude
Neoplasm Metastasis*
Receptors, Vascular Endothelial Growth Factor
Research Design
Salivary Glands*
Treatment Failure
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-2
Vascular Endothelial Growth Factor Receptor-3
Angiogenesis Inducing Agents
Antibodies
Endothelial Growth Factors
Fibroblast Growth Factor 2
Interleukins
Receptors, Vascular Endothelial Growth Factor
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-2
Vascular Endothelial Growth Factor Receptor-3