Browse > Article

EXPRESSIONS OF METASTASIS-RELATED FACTORS IN ORTHOTOPIC TUMOR MODELS OF ORAL SQUAMOUS CELL CARCINOMA  

Park, Young-Wook (Department of Oral and Maxillofacial Surgery, College of Dentistry, Kangnung National University)
Lee, Jong-Won (Department of Oral and Maxillofacial Surgery, College of Dentistry, Kangnung National University)
Kim, So-Hee (Department of Pharmacology, College of Dentistry, Kangnung National University)
Publication Information
Maxillofacial Plastic and Reconstructive Surgery / v.30, no.6, 2008 , pp. 529-539 More about this Journal
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.
Keywords
Oral squamous cell carcinoma; Lymph node metastasis; Metastasis-related factors; Mouth floor model;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Ho CM, Lam KH, Wei W et al : Occult lymph node metastasis in small oral tongue cancers. Head Neck 14 : 359, 1992   DOI   ScienceOn
2 Hannen EJ, Riediger D : The quantification of angiogenesis in relation to metastasis in oral cancer: a review. Int J Oral Maxillofac Surg 33(1) : 2, 2004   DOI   ScienceOn
3 Fidler IJ, Ellis LM : The implications of angiogenesis for the biology and therapy of cancer metastasis. Cell 79 : 185, 1994   DOI   ScienceOn
4 Rajesh V, David S, Jeffery D et al : Expression of vascular endothelial growth factor receptors on tumor cells in head and neck squamous cell carcinoma. Arch Otolaryn Head Neck Surg 129 : 882, 2003   DOI   ScienceOn
5 Ullrich A, Schlessinger J : Signal transduction by receptors with tyrosine kinase activity. Cell 61 : 203, 1990   DOI   ScienceOn
6 Magkou C, Nakopoulou L, Zoubouli C et al : Expression of the epidermal growth factor receptor (EGFR) and the phosphorylated EGFR in invasive breast carcinomas. Breast Cancer Res 10(3) : R49, 2007
7 Park YW, In YS : Immunohistochemical assays for the expression of angiogenic signaling molecules and microvessel density in adenoid cystic carcinomas of human salivary glands. J Kor Assoc Oral Maxillofac Surg 32 : 530, 2006   과학기술학회마을
8 Bei R, Budillon A, Masuelli L et al : Frequent overexpression of multiple ErbB receptors by head and neck squamous cell carcinoma contrasts with rare antibody immunity in patients. Journal of Pathology, 204 : 317, 2004   DOI   ScienceOn
9 Abu-Ali S, Fotovati A, Shirasuna K : Tyrosine-kinase inhibition results in EGFR clustering at focal adhesions and consequent exocytosis in uPAR down-regulated cells of head and neck cancers. Mol Cancer 7 : 47, 2008   DOI   ScienceOn
10 Kim S, Park YW, Schiff BA et al : An orthotopic model of anaplastic thyroid carcinoma in athymic nude mice. Clin Cancer Res 8 : 293, 2002   PUBMED
11 Moriyama M, Kumagai S, Kawashiri K et al : Immunohistochemical study of tumour angiogenesis in oral squamous cell carcinoma. Oral Oncol 33(5) : 369, 1997   DOI   ScienceOn
12 Breiteneder-Geleff S, Soleiman A, Kowalski H et al : Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries: podoplanin as a specific marker for lymphatic endothelium. Am J Pathol 154 : 385, 1999   DOI   PUBMED   ScienceOn
13 Sano D, Myers JN : Metastasis of squamous cell carcinoma of the oral tongue. Cancer Metastasis Rev 26 : 645, 2007   DOI
14 Park YW, Younes MN, Jasser SA et al : AEE788, a dual tyrosine kinase receptor inhibitor, induces endothelial cell apoptosis in human cutaneous squamous cell carcinoma xenografts in nude mice. Clin Cancer Res 11 : 1963, 2005   DOI   ScienceOn
15 Park YW, Chung SH : An experimental study for establishment of orthotopic salivary tumor models in mice. J Kor Oral Maxillofac Surg 33(2) : 81, 2007   과학기술학회마을
16 Sticht C, Freier K, Knopfle K et al : Activation of MAP kinases signaling through ERK5 but not ERK1 expression is associated with lymph node metastases in oral squamous cell carcinoma (OSCC). Neoplasia 10 : 462, 2008   DOI   PUBMED
17 Maual SM, Luukkaa M, Grenman R et al : Intratumoral lymphatics are essential for the metastatic spread and prognosis in squamous cell carcinomas of the head and neck region. Cancer Res 63 : 1920, 2003   PUBMED
18 Grandi C, Alloisio M, Moglia D et al : Prognostic significance of lymphatic spread in head and neck carcinomas: Therapeutic implications. Head Neck Surg 8 : 67, 1985   DOI
19 Stacker SA, Williams RA, Achen MG : Lymphangiogenic growth factors as markers of tumor metastasis. APMIS 112 : 539, 2004   DOI   ScienceOn
20 Mustonen T, Alitalo K : Endothelial receptor tyrosine kinases involved in angiogenesis. J Cell Biol 129(4) : 895, 1995   DOI
21 Van Trappen PO, Steele D, Lowe DG et al : Expression of vascular endothelial growth factor (VEGF)-C and VEGFD, and their receptor VEGFR-3, during different stages of cervical carcinogenesis. J Pathol 201 : 544, 2003   DOI   ScienceOn
22 Rodrigues VC, Moss SM, Tuomainen H : Oral cancer in the UK: To screen or not to screen. Oral Oncol 34 : 454, 1998   DOI   ScienceOn
23 Lydiatt DD, Robbins KT, Byers RM et al : Treatment of stage I and II oral tongue cancer. Head Neck 15 : 308, 1993   DOI   ScienceOn
24 Cochran AJ, Morton DL : Management of the ragional lymph nodes in patients with cutaneous malignant melanoma. World J Surg 16 : 214, 1992   DOI
25 Kowalski LP, Medina JE : Nodal metastasis: predictive factors. Otolaryngol Clin North Am. 31 : 621, 1998   DOI
26 Silverman S Jr : Demographics and occurrence of oral and pharyngeal cancers. The outcomes, the trends, the challenge. J Am Dent Assoc 132(Suppl) : 7S, 2001   DOI
27 Folkman J : Angiogenesis in cencer, vascualr, rheumatoid, and other disease. Nature Med 1 : 27, 1995   DOI
28 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
29 Myers JN, Holsinger FC, Jasser SA et al : An orthotopic nude mouse model of oral tongue squamous cell carcinoma. Clin Cancer Res 8 : 293, 2002   PUBMED
30 Neufeld G, Cohen T, Gitay-Goren H : Similarities and differences between the vascular endothelial growth factor (VEGF) splice variants. Cancer Metastasis Rev 15 : 153, 1996   DOI
31 Ohno F, Nakanishi H, Abe A et al : Regional difference in intratumoral lymphangiogenesis of oral squamous cell carcinomas evaluated by immunohistochemistry using D2-40 and podoplanin antibody: an analysis in comparison with angiogenesis. J Oral Pathol Med 36 : 281, 2001
32 Shayan R, Achen MG, Stacker SA : Lymphatic vessels in cancer metastasis: bridging the gaps. Carcinogenesis 27(9) : 1729, 2006   DOI   ScienceOn
33 Sleeman JP : The lymph node as a bridgehead in the metastatic dissemination of tumours. Recent Results Cancer Res 157 : 55, 2000
34 Ang KK, Berkey BA, Tu X et al : Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res 62 : 7350, 2002   PUBMED
35 Parkin DM, Pisani P, Ferlay J : Global cancer statistics. CA. Cancer J Clinicians 49 : 33, 1999   DOI   ScienceOn