J Korean Assoc Maxillofac Plast Reconstr Surg.  2005 Mar;27(2):110-122.

Cellular and molecular characterization of adenoid cystic carcinoma of the salivary glands

• Park YW

Abstract

Adenoid cystic carcinoma (ACC) of salivary glands has a protracted clinical course with perineural invasion, delayed onset of hematogenous metastasis, and poor responses to classical cytotoxic chemotherapic agents. Most deaths from salivary ACC are caused by lung metastases that are resistant to conventional therapy. Therefore, knowledge of cellular properties and tumor-host interactions that influence the dissemination of metastatic cells is important for the design of more effective therapy of salivary cancer. I determined in vitro expression of epidermal growth factor receptor (EGFR) and its downstream effectors and vascular endothelial growth factor receptor (VEGFR)-2 on a human salivary ACC cell line (ACC2). I also evaluated the expression of EGF and VEGF signaling molecules and etastasis-related proteins on human salivary ACC cells orthotopically growing in nude mice. In Western blot and immunohistochemical analyses, EGFR and VEGFR-2 were presented and phosphorylated in ACC2 cells. In human parotid cancer xenografts in nude mice, EGF and VEGF signaling molecules, IL-8, and MMP-9 were expressed at markedly higher levels than in normal parotid tissues. Moreover, tumor-associated endothelial cells of this orthotopic parotid tumor expressed phosphorylated VEGFR-2 and phosphorylated Akt, which is a cell-survival protein. These data show that those biomarkers can be molecular targets for therapy of salivary ACC, which has a propensity for delayed lung metastasis.

Keyword

Salivary adenoid cystic carcinoma; Epidermal growth factor receptor; Vascular endothelial growth factor receptor; Lung metastasis

MeSH Terms

Adenoids*
Animals
Biomarkers
Blotting, Western
Carcinoma, Adenoid Cystic*
Cell Line
Endothelial Cells
Epidermal Growth Factor
Heterografts
Humans
Interleukin-8
Lung
Mice
Mice, Nude
Neoplasm Metastasis
Parotid Neoplasms
Receptor, Epidermal Growth Factor
Receptors, Vascular Endothelial Growth Factor
Salivary Glands*
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-2
Epidermal Growth Factor
Interleukin-8
Receptor, Epidermal Growth Factor
Receptors, Vascular Endothelial Growth Factor
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-2