期刊论文详细信息
BMC Cancer
Animal model of naturally occurring bladder cancer: Characterization of four new canine transitional cell carcinoma cell lines
Kusum Rathore1  Maria Cekanova1 
[1] Department of Small Animal Clinical Sciences, The University of Tennessee, College of Veterinary Medicine, 2407 River Drive A122, Knoxville, TN 37996-4550, USA
关键词: Bladder cancer;    Xenograft;    Canine;    Transitional cell carcinoma;   
Others  :  855452
DOI  :  10.1186/1471-2407-14-465
 received in 2013-09-30, accepted in 2014-06-11,  发布年份 2014
PDF
【 摘 要 】

Background

Development and further characterization of animal models for human cancers is important for the improvement of cancer detection and therapy. Canine bladder cancer closely resembles human bladder cancer in many aspects. In this study, we isolated and characterized four primary transitional cell carcinoma (K9TCC) cell lines to be used for future in vitro validation of novel therapeutic agents for bladder cancer.

Methods

Four K9TCC cell lines were established from naturally-occurring canine bladder cancers obtained from four dogs. Cell proliferation rates of K9TCC cells in vitro were characterized by doubling time. The expression profile of cell-cycle proteins, cytokeratin, E-cadherin, COX-2, PDGFR, VEGFR, and EGFR were evaluated by immunocytochemistry (ICC) and Western blotting (WB) analysis and compared with established human bladder TCC cell lines, T24 and UMUC-3. All tested K9TCC cell lines were assessed for tumorigenic behavior using athymic mice in vivo.

Results

Four established K9TCC cell lines: K9TCC#1Lillie, K9TCC#2Dakota, K9TCC#4Molly, and K9TCC#5Lilly were confirmed to have an epithelial-cell origin by morphology analysis, cytokeratin, and E-cadherin expressions. The tested K9TCC cells expressed UPIa (a specific marker of the urothelial cells), COX-2, PDGFR, and EGFR; however they lacked the expression of VEGFR. All tested K9TCC cell lines confirmed a tumorigenic behavior in athymic mice with 100% tumor incidence.

Conclusions

The established K9TCC cell lines (K9TCC#1Lillie, K9TCC#2Dakota, K9TCC#4Molly, and K9TCC#5Lilly) can be further utilized to assist in development of new target-specific imaging and therapeutic agents for canine and human bladder cancer.

【 授权许可】

   
2014 Rathore and Cekanova; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140722033858170.pdf 2739KB PDF download
91KB Image download
50KB Image download
194KB Image download
55KB Image download
97KB Image download
【 图 表 】

【 参考文献 】
  • [1]Cancer facts and figures 2014 http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2014/index webcite
  • [2]Kurth KH: Diagnosis and treatment of superficial transitional cell carcinoma of the bladder: facts and perspectives. Eur Urol 1997, 31(Suppl 1):10-19.
  • [3]Shapiro A, Gofrit ON, Pizov G, Cohen JK, Maier J: Raman molecular imaging: a novel spectroscopic technique for diagnosis of bladder cancer in urine specimens. Eur Urol 2011, 59(1):106-112.
  • [4]Allard P, Bernard P, Fradet Y, Tetu B: The early clinical course of primary Ta and T1 bladder cancer: a proposed prognostic index. Br J Urol 1998, 81(5):692-698.
  • [5]Mutsaers AJ, Widmer WR, Knapp DW: Canine transitional cell carcinoma. J Vet Intern Med 2003, 17(2):136-144.
  • [6]Norris AM, Laing EJ, Valli VE, Withrow SJ, Macy DW, Ogilvie GK, Tomlinson J, McCaw D, Pidgeon G, Jacobs RM: Canine bladder and urethral tumors: a retrospective study of 115 cases (1980–1985). J Vet Intern Med 1992, 6(3):145-153.
  • [7]Mohammed SI, Knapp DW, Bostwick DG, Foster RS, Khan KN, Masferrer JL, Woerner BM, Snyder PW, Koki AT: Expression of cyclooxygenase-2 (COX-2) in human invasive transitional cell carcinoma (TCC) of the urinary bladder. Cancer Res 1999, 59(22):5647-5650.
  • [8]de Almeida EM P, Piche C, Sirois J, Dore M: Expression of cyclo-oxygenase-2 in naturally occurring squamous cell carcinomas in dogs. J Histochem Cytochem OffJ Histochem Soc 2001, 49(7):867-875.
  • [9]Knapp DW, Richardson RC, Chan TC, Bottoms GD, Widmer WR, DeNicola DB, Teclaw R, Bonney PL, Kuczek T: Piroxicam therapy in 34 dogs with transitional cell carcinoma of the urinary bladder. J Vet Intern Med 1994, 8(4):273-278.
  • [10]Khanna C, Lindblad-Toh K, Vail D, London C, Bergman P, Barber L, Breen M, Kitchell B, McNeil E, Modiano JF, Niemi S, Comstock KE, Ostrander E, Westmoreland S, Withrow S: The dog as a cancer model. Nat Biotechnol 2006, 24(9):1065-1066.
  • [11]Dhawan D, Ramos-Vara JA, Stewart JC, Zheng R, Knapp DW: Canine invasive transitional cell carcinoma cell lines: in vitro tools to complement a relevant animal model of invasive urinary bladder cancer. Urol ncol 2009, 27(3):284-292.
  • [12]MacEwen EG: Spontaneous tumors in dogs and cats: models for the study of cancer biology and treatment. Cancer Metastasis Rev 1990, 9(2):125-136.
  • [13]Kageyama S, Yoshiki T, Isono T, Tanaka T, Kim CJ, Yuasa T, Okada Y: High expression of human uroplakin Ia in urinary bladder transitional cell carcinoma. Jpn J Cancer Res 2002, 93(5):523-531.
  • [14]Olsburgh J, Harnden P, Weeks R, Smith B, Joyce A, Hall G, Poulsom R, Selby P, Southgate J: Uroplakin gene expression in normal human tissues and locally advanced bladder cancer. J Pathol 2003, 199(1):41-49.
  • [15]Matsumoto K, Satoh T, Irie A, Ishii J, Kuwao S, Iwamura M, Baba S: Loss expression of uroplakin III is associated with clinicopathologic features of aggressive bladder cancer. Urology 2008, 72(2):444-449.
  • [16]Wadhwa P, Goswami AK, Joshi K, Sharma SK: Cyclooxygenase-2 expression increases with the stage and grade in transitional cell carcinoma of the urinary bladder. Int Urol Nephrol 2005, 37(1):47-53.
  • [17]Yeh CY, Shin SM, Yeh HH, Wu TJ, Shin JW, Chang TY, Raghavaraju G, Lee CT, Chiang JH, Tseng VS, Lee YC, Shen CH, Chow NH, Liu HS: Transcriptional activation of the Axl and PDGFR-alpha by c-Met through a ras- and Src-independent mechanism in human bladder cancer. BMC Cancer 2011, 11:139. BioMed Central Full Text
  • [18]Colquhoun AJ, Mellon JK: Epidermal growth factor receptor and bladder cancer. Postgrad Med J 2002, 78(924):584-589.
  • [19]Verma A, Degrado J, Hittelman AB, Wheeler MA, Kaimakliotis HZ, Weiss RM: Effect of mitomycin C on concentrations of vascular endothelial growth factor and its receptors in bladder cancer cells and in bladders of rats intravesically instilled with mitomycin C. BJU Int 2011, 107(7):1154-1161.
  • [20]Smith NR, Baker D, James NH, Ratcliffe K, Jenkins M, Ashton SE, Sproat G, Swann R, Gray N, Ryan A, Jurgensmeier JM, Womack C: Vascular endothelial growth factor receptors VEGFR-2 and VEGFR-3 are localized primarily to the vasculature in human primary solid cancers. Clin Cancer Res 2010, 16(14):3548-3561.
  • [21]Cekanova M, Uddin MJ, Bartges JW, Callens A, Legendre AM, Rathore K, Wright L, Carter A, Marnett LJ: Molecular imaging of cyclooxygenase-2 in canine transitional cell carcinomas in vitro and in vivo. Cancer Prev Res (Philadelphia, Pa) 2013, 6(5):466-476.
  • [22]Komhoff M, Guan Y, Shappell HW, Davis L, Jack G, Shyr Y, Koch MO, Shappell SB, Breyer MD: Enhanced expression of cyclooxygenase-2 in high grade human transitional cell bladder carcinomas. Am J Pathol 2000, 157(1):29-35.
  • [23]Lerner SP, Schoenberg MP, Sternberg CN: Textbook of Bladder Cancer: Taylor and Francis. 2006.
  • [24]Paoloni M, Khanna C: Translation of new cancer treatments from pet dogs to humans. Nat Rev Cancer 2008, 8(2):147-156.
  • [25]Knapp DW, Waters DJ: Naturally occurring cancer in pet dogs: important models for developing improved cancer therapy for humans. Mol Med Today 1997, 3(1):8-11.
  • [26]Loisel S, Ohresser M, Pallardy M, Dayde D, Berthou C, Cartron G, Watier H: Relevance, advantages and limitations of animal models used in the development of monoclonal antibodies for cancer treatment. Critical Rev Oncol/hematol 2007, 62(1):34-42.
  • [27]Henry CJ: Management of transitional cell carcinoma. Vet Clin North Am Small Anim Pract 2003, 33(3):597-613.
  • [28]Knapp DW, Glickman NW, Widmer WR, DeNicola DB, Adams LG, Kuczek T, Bonney PL, DeGortari AE, Han C, Glickman LT: Cisplatin versus cisplatin combined with piroxicam in a canine model of human invasive urinary bladder cancer. Cancer Chemother Pharmacol 2000, 46(3):221-226.
  • [29]Boria PA, Glickman NW, Schmidt BR, Widmer WR, Mutsaers AJ, Adams LG, Snyder PW, DiBernardi L, de Gortari AE, Bonney PL, Knapp DW: Carboplatin and piroxicam therapy in 31 dogs with transitional cell carcinoma of the urinary bladder. Vet Comp Oncol 2005, 3(2):73-80.
  • [30]Uddin MJ, Crews BC, Blobaum AL, Kingsley PJ, Gorden DL, McIntyre JO, Matrisian LM, Subbaramaiah K, Dannenberg AJ, Piston DW, Marnett LJ: Selective visualization of cyclooxygenase-2 in inflammation and cancer by targeted fluorescent imaging agents. Cancer Res 2010, 70(9):3618-3627.
  • [31]Rathore K, Alexander M, Cekanova M: Piroxicam inhibits Masitinib-induced cyclooxygenase 2 expression in oral squamous cell carcinoma cells in vitro. Transl Res J Lab Clinical Med 2014. doi:10.1016/j.trsl.2014.02.002
  文献评价指标  
  下载次数:78次 浏览次数:36次