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Subcutaneous and orthotopic xenograft models of human bladder carcinoma in nude mice for epidermal growth factor receptor-targeted treatment

https://doi.org/10.17650/1726-9784-2018-17-2-31-40

Abstract

Introduction. Approaches based on the principles of a targeted therapy are considered a promising strategy that is capable to improve the effectiveness of treatment for bladder cancer (BC) patients.

The purpose of the study was to establish an orthotopic xenograft model of human BC in mice and to prove its suitability for experimental examination of drugs targeting the epidermal growth factor receptor (EGFR).

Materials and methods. The objects of the study were ectopic subcutaneous and orthotopic human BC xenografts established using EJ and 5637 human BC cell lines. The growth of orthotopic xenografts in vivo was assessed by magnetic resonance imaging. Tumor tissues were investigated using histological and immunohistochemical techniques.

Results. It was shown that EJ and 5637 xenografts exhibit a good reproducibility, a sufficient blood supply of the tumor tissues, a high level of EGFR expression, and different pattern of a subcellular receptor localization. Implantation and subsequent proliferation of human EJ or 5637 cells in the murine bladder mucosa presumably results in muscle-non-invasive tumor formation.

Conclusions. The EJ and 5637 xenograft models can be useful for investigation of the efficacy of EGFR-targeted biotherapeutic treatments.

About the Authors

M. S. Vorontsova
P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Center of Radiology, Ministry of Health of Russia
Russian Federation

3 2nd Botkinskiy Proezd, Moscow 125284



T. A. Karmakova
P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Center of Radiology, Ministry of Health of Russia
Russian Federation

3 2nd Botkinskiy Proezd, Moscow 125284



E. A. Plotnikova
P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Center of Radiology, Ministry of Health of Russia
Russian Federation

3 2nd Botkinskiy Proezd, Moscow 125284



N. B. Morozova
P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Center of Radiology, Ministry of Health of Russia
Russian Federation

3 2nd Botkinskiy Proezd, Moscow 125284



M. A. Abakumov
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia; National University of Science and Technology “MISiS”
Russian Federation

1 Ostrovitianovаst., Moscow 117997, 

4 Leniskiy Prospekt, Moscow 119094



R. I. Yakubovskaya
P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Center of Radiology, Ministry of Health of Russia
Russian Federation

3 2nd Botkinskiy Proezd, Moscow 125284



B. Ya. Alexeev
P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Center of Radiology, Ministry of Health of Russia
Russian Federation

3 2nd Botkinskiy Proezd, Moscow 125284



References

1. Malignant tumors in Russia in 2015 (morbidity and mortality). Ed. A.D. Kaprin, V.V. Starinskiy, G.V. Petrova. Moscow: Hertsen MORI, branch of NMRRC MH RF. 2017. 250 p. (In Russ.)

2. Torre L.A., Siegel R.L., Ward E.M., Jemal A. Global cancer incidence and mortality rates and trends – an update. Cancer Epidemiol Biomarkers Prev 2016;25:16–27. DOI: 10.1158/1055-9965.EPI-15-0578. PMID: 26667886.

3. Alekseev B.Ya., Andreeva Yu.Yu., Novikova I.V. Factors predicting survival in patients with nonmuscle invasive bladder cancer. Onkourologiya = Oncourology 2013;9(1):34–42 (In Russ.)

4. Chou R., Selph S., Buckley D.I. et al. Intravesical therapy for the treatment of nonmuscle invasive bladder cancer: A systematic review and meta-analysis. J Urol 2017;197(5):1189–99. DOI: 10.1016/j.juro.2016.12.090. PMID: 28027868.

5. Komyakov B.K., Guliev B.G., Sergeev A.V. Survival of patients with bladder cancer after radical cystectomy. Onkourologiya = Oncourology 2016;12(1):29–35 (In Russ.)

6. Lobo N., Mount C., Omar K. et al. Landmarks in the treatment of muscleinvasive bladder cancer. Nat Rev Urol 2017;14(9):565–74. DOI: 10.1038/nrurol.2017.82. PMID: 28675174.

7. Sanli O., Dobruch J., Knowles M.A. et al. Bladder cancer. Nat Rev Dis Primers 2017;3:17022. DOI: 10.1038/nrdp.2017.22. PMID: 28406148.

8. Ghosh M., Brancato S.J., Agarwal P.K., Apolo A.B. Targeted therapies in urothelial carcinoma. Curr Opin Oncol 2014;26(3):305–20. DOI: 10.1097/CCO.0000000000000064. PMID: 24685646.

9. Weintraub M.D., Vourganti S., Li Q. et al. Targeting the epidermal growth factor receptor in bladder cancer. J Carcinogene Mutagene 2013;4:143. DOI: 10.4172/2157–2518.1000143.

10. Mooso B.A., Vinall R.L., Mudryj M. et al. The role of EGFR family inhibitors in muscle invasive bladder cancer: a review of clinical data and molecular evidence. J Urol 2015;193(1):19–29. DOI: 10.1016/j.juro.2014.07.121. PMID: 25158272.

11. Chaux A., Cohen J.S., Schultz L. et al. High epidermal growth factor receptor immunohistochemical expression in urothelial carcinoma of the bladder is not associated with EGFR mutations in exons 19 and 21: a study using formalin-fixed, paraffin-embedded archival tissues. Hum. Pathol 2012;43(10):1590–5. DOI: 10.1016/j.humpath.2011.11.016. PMID: 22406363.

12. Carlsson J., Wester K., De La Torre M. et al. EGFR-expression in primary urinary bladder cancer and corresponding metastases and the relation to HER2-expression. On the possibility to target these receptors with radionuclides. Radiol Oncol 2015;49(1):50–8. DOI: 0.2478/raon-2014–0015. PMID: 25810701.

13. Hussain M., Daignault S., Agarwal N. et al. A randomized phase 2 trial of gemcitabine/cisplatin with or without cetuximab in patients with advanced urothelial carcinoma. Cancer 2014;120(17):2684–93. DOI: 10.1002/cncr.28767. PMID: 24802654.

14. Miller K., Morant R., Stenzl A. et al. A phase II study of the Central European Society of Anticancer-Drug Research (CESAR) Group: Results of an openlabel study of gemcitabine plus cisplatin with or without concomitant or sequential gefitinib in patients with advanced or metastatic transitional cell carcinoma of the urothelium. Urol Int 2016;96(1):5–13. DOI: 10.1159/000381589. PMID: 26068576.

15. Powles T., Huddart R.A., Elliott T. et al. Phase III, double-blind, randomized trial that compared maintenance lapatinib versus placebo after first-line chemotherapy in patients with human epidermal growth factor receptor 1/2-positive metastatic bladder cancer. J Clin Oncol 2017;35(1):48–55. DOI: 10.1200/JCO.2015.66.3468. PMID: 28034079.

16. Pfost B., Seidl C., Autenrieth M. et al. Intravesical alpha-radioimmunotherapy with 213Bi-anti-EGFR-mAb defeats human bladder carcinoma in xenografted nude mice. J Nucl Med 2009;50(10): 1700–8. DOI: 10.2967/jnumed.109.065961. PMID: 19793735.

17. Yang X., Kessler E., Su L.J. et al. Diphtheria toxin-epidermal growth factor fusion protein DAB389EGF for the treatment of bladder cancer. Clin Cancer Res 2013;19(1):148–57. DOI: 10.1158/1078-0432.CCR-12-1258. PMID: 23172881.

18. Grivas P.D., Day K.C., Karatsinides A. et al. Evaluation of the antitumor activity of dacomitinib in models of human bladder cancer. Mol Med 2013;19:367–76. DOI: 10.2119/molmed.2013.00108. PMID: 24166682.

19. Tsai Y.C., Ho P.Y., Tzen K.Y. et al. Synergistic blockade of EGFR and HER2 by new-generation EGFR tyrosine kinase inhibitor enhances radiation effect in bladder cancer cells. Mol Cancer Ther 2015;14(3):810–20. DOI: 10.1158/1535-7163.MCT-130951. PMID: 25589492.

20. Railkar R., Krane L.S., Li Q.Q. et al. Epidermal growth factor receptor (EGFR) targeted photoimmunotherapy (PIT) for the treatment of EGFR expressing bladder cancer. Mol Cancer Ther 2017;16(10):2201–14. DOI: 10.1158/1535-7163.MCT-160924. PMID: 28619755.

21. Arantes-Rodrigues R., Colaço A., Pinto-Leite R. et al. In vitro and in vivo experimental models as tools to investigate the efficacy of antineoplastic drugs on urinary bladder cancer. Anticancer Res 2013;33(4):1273–96. PMID: 23564765.

22. Dominguez-Escrig J.L., Kelly J.D., Neal D.E. et al. Evaluation of the therapeutic potential of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib in preclinical models of bladder cancer. Clin Cancer Res 2004;10(14):4874–84. DOI: 10.1158/1078-0432.CCR-04-0034. PMID: 15269164.

23. Mansure J.J., Nassim R., Chevalier S. et al. A novel mechanism of PPAR gamma induction via EGFR signalling constitutes rational for combination therapy in bladder cancer. PLoS One 2013;8(2):e55997. DOI: 10.1371/journal.pone.0055997. PMID: 23409107.

24. Bhuvaneswari R., Gan Y.Y., Soo K.C., Olivo M. Targeting EGFR with photodynamic therapy in combination with Erbitux enhances in vivo bladder tumor response. Mol Cancer 2009;8:94. DOI: 10.1186/1476-4598-8-94. PMID: 19878607.

25. Wu M.L., Li H., Yu L.J. et al. Short-term resveratrol exposure causes in vitro and in vivo growth inhibition and apoptosis of bladder cancer cells. PLoS One 2014;9(2):e89806. DOI: 10.1371/journal.pone.0089806. PMID: 24587049.

26. Fazel J., Rötzer S., Seidl C. et al. Fractionated intravesical radio immunotherapy with (213) Bi-anti-EGFR-MAb is effective without toxic side-effects in a nude mouse model of advanced human bladder carcinoma. Cancer Biol Ther 2015;16(10):1526–34. DOI: 10.1080/15384047.2015.1071735. PMID: 26177233.

27. Guidelines for laboratory animals and alternative models in biomedical research. Ed. N.N. Karkishchenko, S.V. Grachev. Moscow: Profil-2S Ltd, 2010. 358 p. (In Russ.)

28. Chan E., Patel A., Heston W., Larchian W. Mouse orthotopic models for bladder cancer research. BJU Int 2009;104(9):1286–91. DOI: 10.1111/j.1464-410X.2009.08577.x. PMID: 19388981.

29. Einama T., Ueda S., Tsuda H. et al. Membranous and cytoplasmic expression of epidermal growth factor receptor in metastatic pancreatic ductal adenocarcinoma. Exp Ther Med 2012;3:931–36. DOI: 10.3892/etm.2012.518. PMID: 22969995.

30. Ueda S., Ogata S., Tsuda H. et al. The correlation between cytoplasmic overexpression of epidermal growth factor receptor and tumor aggressiveness: poor prognosis in patients with pancreatic ductal adenocarcinoma. Pancreas 2004;29:e1–8. PMID: 15211117.

31. Kankaya D., Kiremitci S., Tulunay O., Baltaci S. Prognostic impact of epidermal growth factor receptor on clear cell renal cell carcinoma: Does it change with different expression patterns? Indian Journal of Pathology and Microbiology 2016;59:35–40. DOI: 10.4103/0377-4929.178219. PMID: 26960632.

32. Kallio J.P., Hirvikoski P., Helin H. et al. Membranous location of EGFR immunostaining is associated with good prognosis in renal cell carcinoma. Br J Cancer 2003;89:1266–9. DOI: 10.1038/sj.bjc.6601241. PMID: 14520458.

33. Tomas A., Futter C.E., Eden E.R. EGF receptor trafficking: consequences for signaling and cancer. Trends Cell Biol 2014;24(1):26–34. DOI: 10.1016/j.tcb.2013.11.002. PMID: 24295852.

34. Pirker R., Pereira J.R., von Pawel J. et al. EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study. The Lancet Oncology. 2012;13:33–42. DOI: 10.1016/S1470-2045(11)70318-7. PMID: 22056021


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Vorontsova M.S., Karmakova T.A., Plotnikova E.A., Morozova N.B., Abakumov M.A., Yakubovskaya R.I., Alexeev B.Ya. Subcutaneous and orthotopic xenograft models of human bladder carcinoma in nude mice for epidermal growth factor receptor-targeted treatment. Russian Journal of Biotherapy. 2018;17(2):31-40. (In Russ.) https://doi.org/10.17650/1726-9784-2018-17-2-31-40

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