Browse > Article

CELLULAR AND MOLECULAR CHARACTERIZATION OF ADENOID CYSTIC CARCINOMA OF THE SALIVARY GLANDS  

Park, Young-Wook (Department of Oral and Maxillofacial Surgery, College of Dentistry, Kangnung National University)
Publication Information
Maxillofacial Plastic and Reconstructive Surgery / v.27, no.2, 2005 , pp. 110-122 More about this Journal
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 metastasis-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.
Keywords
Salivary adenoid cystic carcinoma; Epidermal growth factor receptor; Vascular endothelial growth factor receptor; Lung metastasis;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Spiro RH : Salivary neoplasms, overview of a 35 year experience with 2,807 patients. Head Neck Surg 8 : 177, 1986   DOI   PUBMED   ScienceOn
2 Airoldi M, Fornari G, Pedani F et al : Paclitaxel and carboplatin for recurrent salivary gland malignancies. Anticancer Res 20(5C) : 3781, 2000   PUBMED
3 Holsinger FC, Doan DD, Jasser SA, et al. Epidermal growth factor receptor blockade potentiates apoptosis mediated by paclitaxel and leads to prolonged survival in a murine model of oral cancer. Clin Cancer Res 9 : 3183-9, 2003   PUBMED
4 Esser S, Wolburg K, Wolburg H et al : Vascular endothelial growth factor induces endothelial fenestrations in vitro. J Cell Biol 140 : 947, 1998   DOI   ScienceOn
5 Ferrara N, Houck K, Jakeman L et al : Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev 13 : 18, 1992   PUBMED
6 Sauter ER, Nesbit M, Watson JC, et al. Vascular endothelial growth factor is a marker of tumor invasion and metastasis in squamous cell carcinoma of the head and neck. Clin Cancer Res 1999; 5: 775-82   PUBMED
7 Killion JJ, Radinsky R, Fidler IJ : Orthotopic models are necessary to predict therapy of transplantable tumors in mice. Cancer Metas Rev 17 : 279, 1999
8 Spiro RH : Salivary neoplasms, overview of a 35 year experience with 2,807 patients. Head Neck Surg 8 : 177, 1986   DOI   PUBMED   ScienceOn
9 Herbst RS, Langer CJ : Epidermal growth factor receptors as a target for cancer treatment: the emerging role of IMC-C225 in the treatment of lung and head and neck cancers. Semin Oncol 29 : 27, 2002   PUBMED
10 Neuchrist C, Quint C, Pammer A et al : Vascular endothelial growth factor (VEGF) and microvessel density in squamous cell carcinomas of the larynx: an immunohistochemical study. Acta Otolaryngol 119 : 732, 1999   DOI   PUBMED   ScienceOn
11 Ishibashi H, Shiratuchi T, Nakagawa K et al : Hypoxiainduced angiogenesis of cultured human salivary gland carcinoma cells enhances vascular endothelial growth factor production and basic fibroblast growth factor release. Oral Oncol 37 : 77, 2001   DOI   ScienceOn
12 Bergers G, Brekken R, McMahon G et al : Matrix metalloproteinase- 9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2 : 737, 2000   DOI   ScienceOn
13 Craven RJ, Lightfoot H, Cance WG : A decade of tyrosine kinases: from gene discovery to therapeutics. Surg Oncol 12 : 39, 2003   DOI   ScienceOn
14 Cohen EE, Rosen F, Stadler WM et al : Phase II trial of ZD1839 in recurrent or metastatic squamous cell carcinoma of the head and neck. J Clin Oncol 21: 1980, 2003   DOI   ScienceOn
15 Luca M, Huang S, Gershenwald JE et al : Expression of interleukin-8 by human melanoma cells up-regulates MMP-2 activity and increases tumor growth and metastasis. Am J Pathol 151 : 41, 1997
16 Koch AE, Polverini PJ, Kunkel SL et al : Interleukin-8 as a macrophage derived mediator of angiogenesis. Science 258 : 1798, 1992   DOI   PUBMED
17 Khazaie K, Schirrmacher V, Lichtner RB : EGF receptor in neoplasia and metastasis. Cancer Metastasis Rev 12 : 255, 1993   DOI   ScienceOn
18 Radinsky R, Risin S, Fan D et al : Level and function of epidermal growth factor receptor predict the metastatic potential of human colon carcinoma cells. Clin Cancer Res 1 : 19, 1995
19 Kawashima M : Chemoradiotherapy for head and neck cancer: current status and perspectives. Int J Clin Oncol 9 : 421, 2004   DOI   ScienceOn
20 Yigitbasi OG, Younes MN, Doan D et al : Tumor cell and endothelial cell therapy of oral cancer by dual tyrosine kinase receptor blockade. Cancer Res 64 : 7977, 2004   DOI   ScienceOn
21 Baselga J, Rischin D, Ranson M et al : Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types. J Clin Oncol 20 : 4292, 2002   DOI   ScienceOn
22 Fordice J, Kershaw C, El-Naggar et al : Adenoid cystic carcinoma of the head and neck: predictors of morbidity and mortality. Arch Otolaryngol Head Neck Surg 125 : 149, 1999   PUBMED
23 Obermair A, Kohlberger P, Bancher-Todesca D et al : Influence of microvessel density and vascular permeability factor/ vascular endothelial growth factor expression on prognosis in vulvar cancer. Gynecol Oncol 63 : 204, 1996   DOI   ScienceOn
24 Chang C, Werb Z : The many faces of metalloproteases: cell growth, invasion, angiogenesis and metastasis. Trends in Cell Biol 11 : S37, 2001
25 Yu F, Jiang XZ, Chen WT et al : Microvessel density and expression of vascular endothelial growth factor in adenoid cystic carcinoma of salivary gland. Shanghai Kou Qiang Yi Xue 12 : 443, 2003   PUBMED
26 Kubota T : Metastatic models of human cancer xenografted in mice: the importance of orthotopic transplantation. J Cell Biochem 56 : 4, 1994   DOI   PUBMED   ScienceOn
27 Dong Z, Radinsky R, Fan D et al : Organ-specific modulation of steady-state mdr gene expression and drug resistance in murine colon carcinoma cell line. J Natl Cancer Inst 86 : 913, 1994   DOI   ScienceOn
28 Gille J, Swerlick RA, Caughman SW : Transforming growth factor-alpha-induced transcriptional activation of the vascular permeability factor (VPF/VEGF) gene requires AP-2-dependent DNA binding and transactivation. Embo J 16 : 750, 1997   DOI   PUBMED   ScienceOn
29 de Jong JS : Expression of growth factors, growth-inhibiting factors, and their receptors in invasive breast cancer. II: Correlations with proliferation and angiogenesis. J Pathol 184 : 53, 1998   DOI   ScienceOn
30 Barnes CJ, Bagheri-Yarmand R, Mandal M et al : Suppression of epidermal growth factor receptor, mitogenactivated protein kinase, and Pak1 pathway and invasiveness of human cutaneous squamous cancer cells by the tyrosine kinase inhibitor ZD1839 (Iressa). Mol Cancer Ther 2 : 345, 2003   PUBMED
31 Goldman CK : Epidermal growth factor stimulates vascular endothelial growth factor production by human malignant glioma cells: a model of glioblastoma multiforme pathophysiology. Mol Biol Cell 4 : 121, 1993   PUBMED
32 Rusch V : Overexpression of the epidermal growth factor receptor and its ligand transforming growth factor alpha is frequent in resectable non-small cell lung cancer but does not predict tumor progression. Clin Cancer Res 3 : 515, 1997   PUBMED
33 Fu XY, Theodorescu D, Kerbel RS et al : Extensive multiorgan metastasis following orthotopic implantation of histologically- intact human bladder carcinoma tissue in nude mice. Int J Cancer 49 : 938, 1991   DOI   PUBMED
34 Vered M, Braunstein E, Buchner A : Immunohistochemical study of epidermal growth factor receptor in adenoid cystic carcinoma of salivary gland origin. Head Neck 24 : 632, 2002   DOI   ScienceOn
35 Fidler IJ, Wilmanns C, Staroselsky A et al : Modulation of tumor cell reponse to chemotherapy by the organ environment. Cancer Metastasis Rev 13 : 209, 1994   DOI   ScienceOn
36 Ang KK, Andratschke NH, Milas L : Epidermal growth factor receptor and response of head-and-neck carcinoma to therapy. Int J Radiat Oncol Biol Phys 58 : 959, 2004   DOI   ScienceOn
37 Bowden J, Brennan PA, Umar T et al : Expression of vascular endothelial growth factor in basal cell carcinoma and cutaneous squamous cell carcinoma of the head and neck. J Cutan Pathol 29 : 585, 2002   DOI   ScienceOn
38 Fidler IJ : Rationale and methods for the use of nude mice to study the biology and therapy of human cancer metastasis. Cancer Metastasis Rev 5 : 29, 1986   DOI   ScienceOn