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http://dx.doi.org/10.14402/jkamprs.2013.35.1.001

Effect of Lymphangiogenic Factors on Survival in a Murine Model of Oral Squamous Cell Carcinoma  

Park, Young-Wook (Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University)
Cho, Ju-Won (Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University)
Publication Information
Maxillofacial Plastic and Reconstructive Surgery / v.35, no.1, 2013 , pp. 1-12 More about this Journal
Abstract
Purpose: Vascular endothelial growth factor (VEGF)-C and its tyrosine kinase receptor, VEGF receptor (VEGFR)-3 are recently known to have lymphangiogenic activities in various tumor types. In this study, we determined whether the expression of lymphangiogenic factors correlate with nodal metastasis or survival in a nude mouse model of oral squamous cell carcinoma (OSCC). Methods: Three OSCC cells (KB, SCC4, SCC9) were xenografted into the right mandibular gland of athymic nude mice. The mice were followed for tumor development and growth, and the mice were sacrificed when they had lost more than 20% of their initial body weight, or the diameter of the induced tumor exceeds 20 mm. After necropsy, the murine tumors were examined histologically and radiologically (micro-positron emission tomography computed tomography) for regional or distant metastasis. We performed immunohistochemical assays with anti-VEGF-C, VEGFR-3, CD105, and D2-40 antibodies. Immunofluorescence double staining for LYVE-1/CD31 was also performed. To quantify the VEGF-C and VEGFR-3 level in the cancer tissue, Western blotting was performed. Finally, we determined the correlation between the degree of expression of VEGF-C/VEGFR-3 and the mean survival time. Results: OSCC tumor cells into the mandibular gland of the nude mice successfully resulted in the formation of recapitulating orthotopic tumor. Tumor cells of the induced tumor did not express VEGF-C. VEGF-C/VEGFR-3 expression was mainly distributed in the endothelial cells of the stromal area. There were no correlation between the degree of expression of VEGF-C/VEGFR-3 and the mean survival time of mice injected with different OSCC cell lines. Conclusion: An recapitulating orthotopic model of OSCC in nude mice was established, which copies the cervical nodal metastasis of human OSCC. Overexpression of lymphangiogenic factors seems to have no effect on survival of hosts in this in vivo experiment.
Keywords
Oral squamous cell carcinoma; Recapitulating orthotopic nude mouse model; Lymphangiogenic factor; Survival study;
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1 Parkin DM, Pisani P, Ferlay J. Global cancer statistics. CA Cancer J Clin 1999;49:33-64, 1.   DOI   ScienceOn
2 Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 2005;23:1011-27.   DOI
3 Shibuya M, Claesson-Welsh L. Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis. Exp Cell Res 2006;312:549-60.   DOI   ScienceOn
4 Bock JM, Sinclair LL, Bedford NS, Jackson RE, Lee JH, Trask DK. Modulation of cellular invasion by VEGF-C expression in squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 2008;134:355-62.   DOI   ScienceOn
5 Neuchrist C, Erovic BM, Handisurya A, et al. Vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 expression in squamous cell carcinomas of the head and neck. Head Neck 2003;25:464-74.   DOI   ScienceOn
6 Smith BD, Smith GL, Carter D, Sasaki CT, Haffty BG. Prognostic significance of vascular endothelial growth factor protein levels in oral and oropharyngeal squamous cell carcinoma. J Clin Oncol 2000;18:2046-52.   DOI
7 Tae K, El-Naggar AK, Yoo E, et al. Expression of vascular endothelial growth factor and microvessel density in head and neck tumorigenesis. Clin Cancer Res 2000;6:2821-8.
8 Kyzas PA, Cunha IW, Ioannidis JP. Prognostic significance of vascular endothelial growth factor immunohistochemical expression in head and neck squamous cell carcinoma: a meta-analysis. Clin Cancer Res 2005;11:1434-40.   DOI   ScienceOn
9 Stacker SA, Williams RA, Achen MG. Lymphangiogenic growth factors as markers of tumor metastasis. APMIS 2004; 112:539-49.   DOI   ScienceOn
10 He Y, Rajantie I, Pajusola K, et al. Vascular endothelial cell growth factor receptor 3-mediated activation of lymphatic endothelium is crucial for tumor cell entry and spread via lymphatic vessels. Cancer Res 2005;65:4739-46.   DOI   ScienceOn
11 Warburton G, Nikitakis NG, Roberson P, et al. Histopathological and lymphangiogenic parameters in relation to lymph node metastasis in early stage oral squamous cell carcinoma. J Oral Maxillofac Surg 2007;65:475-84.   DOI   ScienceOn
12 Kishimoto K, Sasaki A, Yoshihama Y, Mese H, Tsukamoto G, Matsumura T. Expression of vascular endothelial growth factor-C predicts regional lymph node metastasis in early oral squamous cell carcinoma. Oral Oncol 2003;39:391-6.   DOI   ScienceOn
13 O-charoenrat P, Rhys-Evans P, Eccles SA. Expression of vascular endothelial growth factor family members in head and neck squamous cell carcinoma correlates with lymph node metastasis. Cancer 2001;92:556-68.   DOI   ScienceOn
14 Sedivy R, Beck-Mannagetta J, Haverkampf C, Battistutti W, Honigschnabl S. Expression of vascular endothelial growth factor-C correlates with the lymphatic microvessel density and the nodal status in oral squamous cell cancer. J Oral Pathol Med 2003;32:455-60.   DOI   ScienceOn
15 Wey JS, Stoeltzing O, Ellis LM. Vascular endothelial growth factor receptors: expression and function in solid tumors. Clin Adv Hematol Oncol 2004;2:37-45.
16 Zeng Y, Opeskin K, Baldwin ME, et al. Expression of vascular endothelial growth factor receptor-3 by lymphatic endothelial cells is associated with lymph node metastasis in prostate cancer. Clin Cancer Res 2004;10:5137-44.   DOI   ScienceOn
17 Park YW. Targeted molecular therapy in a murine model of oral squamous cell carcinoma with an epidermal growth factor receptor inhibitor. J Korean Assoc Maxillofac Plast Reconstr Surg 2009;31:8-17.   과학기술학회마을
18 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 2005;11:1963-73.   DOI   ScienceOn
19 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 2004;64:7977-84.   DOI   ScienceOn
20 Grandi C, Alloisio M, Moglia D, et al. Prognostic significance of lymphatic spread in head and neck carcinomas: therapeutic implications. Head Neck Surg 1985;8:67-73.   DOI   ScienceOn
21 Park YW, Kim SG, Kim SH, Kim HS, Kim MK. Gene expression for lymphangiogenic factors in oral mucosal squamous cell carcinoma. J Korean Assoc Maxillofac Plast Reconstr Surg 2009;31:453-60.   과학기술학회마을
22 Park YW, Kim SH. Targeting receptor tyrosine kinase on endothelial cells in an orthotopic tumor model of oral squamous cell carcinorma. J Korean Assoc Oral Maxillofac Surg 2009;35:55-65.   과학기술학회마을
23 Park YW, Kim SG, Choi JY, Lee SK. Recapitulating orthotopic tumor model through establishment of a parotid gland tumor with lung metastasis using HeLa cell injection into nude mice. Oncol Rep 2010;23:701-8.
24 Myers JN, Holsinger FC, Jasser SA, Bekele BN, Fidler IJ. An orthotopic nude mouse model of oral tongue squamous cell carcinoma. Clin Cancer Res 2002;8:293-8.
25 Kim S, Park YW, Schiff BA, et al. An orthotopic model of anaplastic thyroid carcinoma in athymic nude mice. Clin Cancer Res 2005;11:1713-21.   DOI   ScienceOn
26 Younes MN, Park YW, Yazici YD, et al. Concomitant inhibition of epidermal growth factor and vascular endothelial growth factor receptor tyrosine kinases reduces growth and metastasis of human salivary adenoid cystic carcinoma in an orthotopic nude mouse model. Mol Cancer Ther 2006;5: 2696-705.   DOI   ScienceOn
27 Jackson DG, Prevo R, Clasper S, Banerji S. LYVE-1, the lymphatic system and tumor lymphangiogenesis. Trends Immunol 2001;22:317-21.   DOI   ScienceOn
28 Tanaka T, Nakayama H, Yoshitake Y, et al. Selective inhibition of nuclear factor-κB by nuclear factor-κB essential modulator-binding domain peptide suppresses the metastasis of highly metastatic oral squamous cell carcinoma. Cancer Sci 2012;103:455-63.   DOI   ScienceOn
29 Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1995;1:27-31.   DOI   ScienceOn
30 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 1999;154:385-94.   DOI   ScienceOn
31 Lee SW, Park YW. Expression of endoglin and podoplanin in early and advanced oral squamous cell carcinoma. J Korean Assoc Oral Maxillofac Surg 2012;38:145-51.   과학기술학회마을   DOI   ScienceOn
32 Saad RS, Lindner JL, Liu Y, Silverman JF. Lymphatic vessel density as prognostic marker in esophageal adenocarcinoma. Am J Clin Pathol 2009;131:92-8.   DOI   ScienceOn