AN EXPERIMENTAL STUDY FOR ESTABLISHMENT OF ORTHOTOPIC SALIVARY TUMOR MODELS IN MICE

마우스에서 타액선암 동위종양 모델 제작을 위한 실험적 연구

  • Park, Young-Wook (Department of Oral and Maxillofacial Surgery, College of Dentistry, Kangnung National University) ;
  • Chung, Seong-Hoon (Department of Oral and Maxillofacial Surgery, College of Dentistry, Kangnung National University)
  • 박영욱 (강릉대학교 치과대학 구강악안면외과학교실) ;
  • 정성훈 (강릉대학교 치과대학 구강악안면외과학교실)
  • Published : 2007.04.30

Abstract

Purpose: Adenoid cystic carcinoma (ACC) is a relatively rare tumor that arises in glandular tissues of the head and neck region and sometimes has a protracted clinical course with perineural invasion and delayed onset of distant lung metastasis. Treatment failure of salivary ACC is most often associated with perineural and hematogenous tumor spread. However, very little has been known about the cellular and molecular mechanisms of perineural invasion and hematogenous distant metastasis of parotid ACC. This study was designed to develop an orthotopic tumor model of parotid adenoid cystic carcinoma in athymic nude mice. Experimental Design: A melanoma cell line was injected into the parotid gland of athymic mice to determine whether such implantation was technically feasible. A parotid ACC cell line was then injected into the parotid gland or the subcutaneous tissue of athymic mice at various concentrations of tumor cells, and the mice were thereafter followed for development of tumor nodule. The tumors were examined histopathologically for perineural invasion or regional or distant lung metastasis. We used an oral squmous cell carcinoma cell line as control. Results: Implantation of tumor(melanoma) cell suspension into the parotid gland of nude mice was technically feasible and resulted in the formation of parotid tumors. A parotid ACC cell line, ACC3 showed no significantly higher tumorigenicity, but showed significantly higher lung metastatic potential in the parotid gland than in the subcutis. In contrast, mucosal squmous cell carcinoma cell line doesn’t show significantly higher lung metastatic potential in the parotid gland than in the subcutis. The ACC tumor established in the parotid gland seemed to demonstrate perineural invasion of facial nerve, needs further study. Conclusion: An orthotopic tumor model of salivary ACC in athymic nude mice was successfully developed that closely recapitulates the clinical situations of human salivary ACC. This model should facilitate the understanding of the cellular and molecular mechanisms of tumorigenisis and metastasis of salivary ACC and aid in the development of targeted molecular therapies of salivary ACC.

Keywords

References

  1. Stephan Ariyan, Cancer of the head and neck, 1st ed, St. Louis: The C.V. Mosby Co, 1987
  2. Spiro RH: Salivary neoplasms, overview of a 35 year experience with 2,807 patients. Head Neck Surg 1986;8:177 https://doi.org/10.1002/hed.2890080309
  3. Araujo VC, Loducca SV, Sousa SO, Williams DM, Araujo NS: The cribriform features of adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma: cytokeratin and inegrin expression. Ann Diagn Pathol 2001;5:330
  4. Fordice J, Kershaw C, El-Naggar, Goepfert H: Adenoid cystic carcinoma of the head and neck: predictors of morbidity and mortality.? Arch Otolaryngol Head Neck Surg 1999;125:149-152 https://doi.org/10.1001/archotol.125.2.149
  5. Batsakis JG, Luna MA, el-Naggar A: Histopathologic grading of salivary gland neoplasms. III. Adenoid cystic carcinomas. Ann Otol Rhinol Laryngol 1990;99:1007
  6. Nascimento AG, Amaral AL, Prado LA, Kligerman J, Silveira TR: Adenoid cystic carcinoma of salivary glands: a study of 61 cases with clinicopathologic correlation. Cancer 1986;57:312 https://doi.org/10.1002/1097-0142(19860115)57:2<312::AID-CNCR2820570220>3.0.CO;2-A
  7. Maciejewski A, Szymczyk D, Wierzgonn J: Outcome of surgery for adenoid cystic carcinoma of head and neck region. J Craniomaxillofac Surg 2002;30:59 https://doi.org/10.1054/jcms.2001.0265
  8. Kawashima M: Chemoradiotherapy for head and neck cancer: current status and perspectives. Int J Clin Oncol 2004;9:421 https://doi.org/10.1007/s10147-004-0445-x
  9. Fidler IJ: Rationale and methods for the use of nude mice to study the biology and therapy of human cancer metastasis. Cancer Metastasis Rev 1986;5:29-49 https://doi.org/10.1007/BF00049529
  10. Hendrickson EA: The SCID mouse: relevance as an animal model system for studying human disease. Am J Pathol 1993;143:1511
  11. Kubota T: Metastatic models of human cancer xenografted in mice: the importance of orthotopic transplantation. J Cell Biochem 1994;56:4
  12. Khazaie K, Schirrmacher V, Lichtner RB: EGF receptor in neoplasia and metastasis. Cancer Metastasis Rev 1993;12:255 https://doi.org/10.1007/BF00665957
  13. Chang C, Werb Z: The many faces of metalloproteases: cell growth, invasion, angiogenesis and metastasis. Trends in Cell Biol 2001; 11:S376
  14. Barnes CJ, Bagheri-Yarmand R, Mandal M, Yang Z, Clayman GL, Hong WK, et al: Suppression of epidermal growth factor receptor, mitogen-activated protein kinase, and Pak1 pathway and invasiveness of human cutaneous squamous cancer cells by the tyrosine kinase inhibitor ZD1839 (Iressa). Mol Cancer Ther 2003;2:345
  15. Craven RJ, Lightfoot H, Cance WG: A decade of tyrosine kinases: from gene discovery to therapeutics. Surg Oncol 2003;12:39
  16. Ferrara N, Houck K, Jakeman L, Leung DW: Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev 1992;13:18
  17. Esser S, Wolburg K, Wolburg H, Breier G, Kurzchalia T, Risau W: Vascular endothelial growth factor induces endothelial fenestrations in vitro. J Cell Biol 1998;140:947 https://doi.org/10.1083/jcb.140.4.947
  18. Sauter ER, Nesbit M, Watson JC, Clein-Szanto A, Litwins S, Herlyn M: 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;5:775-782
  19. Fu XY, Theodorescu D, Kerbel RS, Hoffman RM: Extensive multiorgan metastasis following orthotopic onplantation of histologicallyintact human bladder carcinoma tissue in nude mice. Int J Cancer 1991;49:938 https://doi.org/10.1002/ijc.2910490623
  20. Killion JJ, Radinsky R, Fidler IJ: Orthotopic models are necessary to predict therapy of transplantable tumors in mice. Cancer Metas Rev 1999;17:279
  21. Umeda M, Komatsubara H, Nishimatsu N, Oku N, Shibuya Y, Yokoo S, et al: Establishment and characterization of a human adenoid cystic carcinoma line of the salivary gland which is serially transplantable and spontaneously metastasises to the lung in nude mice. Oral Oncol 2002 38:30-34 https://doi.org/10.1016/S1368-8375(01)00010-0
  22. Kim S, Park YW, Schiff BA, Doan DD, Yazici Y, Jasser SA, et al: An Orthotopic model of anaplastic thyroid carcinoma. Clin Cancer Res 2005;11:1713-1721 https://doi.org/10.1158/1078-0432.CCR-04-1908
  23. Fidler IJ: Selection of successive tumour lines for metastasis. Nat New Biol 1973;242:148-149 https://doi.org/10.1038/newbio242148a0
  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;8:293-298
  25. Yigitbasi OG, Younes MN, Doan D, Jasser SA, Schiff BA, Bucana CD: Tumor cell and endothelial cell therapy of oral cancer by dual tyrosine kinase receptor blockade. Cancer Res 2004;64:7977-7984 https://doi.org/10.1158/0008-5472.CAN-04-1477
  26. He RG, Zhang XS, Zhou XJ, Wang Z, Zhang XL, Qiu WL: The establishment of human salivary glands (ACC2, ACC3) and a study of morphology. West Chin J Stomatol 1988;6:1-4
  27. Franca CM, Jaeger MMM, Jaeger RG, Arau′jo NS: The role of basement membrane proteins on the expression of neural cell adhesion molecule (N-CAM) in an adenoid cystic carcinoma cell line. Oral Oncol 2000;36:248-252 https://doi.org/10.1016/S1368-8375(99)00087-1
  28. Umeda M, Yokoo S, Komori T, Nishimatsu N, Shibuya Y, Fujioka M: Experimental model of invasion and metastasis by orthotopic transplantation of oral squamous and adenoid cystic carcinomas into the tongue of nude mice. Br J Oral Maxillofac Surg 2001;39:376-380 https://doi.org/10.1054/bjom.2000.0590
  29. Cheng J, Irie T, Munakata R, Kimura S, Nakamura H, He RG, et al: Biosynthesis of basement membrane molecules by salivary adenoid cystic carcinoma cells: an immunofluorescence and confocal microscopic study. Virchows Arch 1995;426:577-586
  30. An Z, Jiang P, Wang X, Moossa AR, Hoffman RM: Development of a high metastatic orthotopic model of human renal cell carcinoma in nude mice: benefits of fragment implantation compared to cell-suspension injection. Clin Exp Metastasis 1999;7:265-270
  31. Holsinger FC, Doan DD, Jasser SA, Swan EA, Greenberg JS, Schiff BA, 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 2003;9:3183-3189
  32. Fidler IJ, Wilmanns C, Staroselsky A, Radinsky R, Dong Z, Fan D: Modulation of tumor cell response to chemotherapy by the organ environment. Cancer Metastasis Rev 1994;13:209 https://doi.org/10.1007/BF00689637
  33. Dinney CP, Fishbeck R, Singh RK, Eve B, Pathak S, Brown N, et al: Isolation and characterization of metastatic variants from human transitional cell carcinoma passaged by orthotopic implantation in athymic nude mice. J Urol 1995;154:1532-1538 https://doi.org/10.1016/S0022-5347(01)66923-4
  34. Bruns CJ, Harbison MT, Kuniyasu H, Eue I, Fidler IJ: In vivo selection and characterization of metastatic variants from human pancreatic adenocarcinoma by using orthotopic implantation in nude mice. Neoplasia 1999;1:50-62 https://doi.org/10.1038/sj.neo.7900005
  35. Lensch R, Gotz C, Andres C, Bex A, Lehmann J, Zwergel T, et al: Compregensive genotypic analysis of human prostate cancer cell lines and sublines derived from metastases after orthotopic implantation in nude mice. Int J Oncol 2002;21:695-706
  36. Airoldi M, Fornari G, Pedani F, Marchionatti S, Gabriele P, Succo G, et al: Paclitaxel and carboplatin for recurrent salivary gland malignancies. Anticancer Res 2000;20:3781