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Cytotoxicity of natural killer cells on canine mammary carcinoma cells

개 유선종양세포에 대한 자연살해세포 독성

  • Jeong, Da-Un (Viral Disease Research Division, Animal and Plant Quarantine Agency) ;
  • Byeon, Jeong Su (Viral Disease Research Division, Animal and Plant Quarantine Agency) ;
  • Gu, Na-Yeon (Viral Disease Research Division, Animal and Plant Quarantine Agency) ;
  • Jung, Moonhee (Department of Forensic Medicine, Chonnam National University Medical School) ;
  • Kim, Eun Hee (Department of Forensic Medicine, Chonnam National University Medical School) ;
  • Kim, Hyung-Seok (Department of Forensic Medicine, Chonnam National University Medical School) ;
  • Cho, In-Soo (Viral Disease Research Division, Animal and Plant Quarantine Agency) ;
  • Song, Jae-Young (Viral Disease Research Division, Animal and Plant Quarantine Agency) ;
  • Hyun, Bang-Hun (Viral Disease Research Division, Animal and Plant Quarantine Agency) ;
  • Lee, Jienny (Viral Disease Research Division, Animal and Plant Quarantine Agency)
  • 정다운 (농림축산검역본부 바이러스질병과) ;
  • 변정수 (농림축산검역본부 바이러스질병과) ;
  • 구나연 (농림축산검역본부 바이러스질병과) ;
  • 정문희 (전남대학교 의과대학 법의학교실) ;
  • 김은희 (전남대학교 의과대학 법의학교실) ;
  • 김형석 (전남대학교 의과대학 법의학교실) ;
  • 조인수 (농림축산검역본부 바이러스질병과) ;
  • 송재영 (농림축산검역본부 바이러스질병과) ;
  • 현방훈 (농림축산검역본부 바이러스질병과) ;
  • 이지현 (농림축산검역본부 바이러스질병과)
  • Received : 2019.06.28
  • Accepted : 2019.12.02
  • Published : 2020.03.31

Abstract

Natural killer (NK) cells play have a crucial role in the early phase of immune responses against various pathogens. We compared characteristics of canine NK cells against two canine mammary carcinoma cell lines, REM134 and CF41.Mg. REM134 showed higher expression of progesterone receptor, proliferative cell nuclear antigen, Ki67, multiple drug resistance, Bmi-1, c-myc, E-cadherin, and human epidermal growth factor receptor type-2 than that of CF41.Mg. For specific expansion and activation of NK cells, we isolated CD5 negative cells from canine peripheral blood mononuclear cells and co-cultured K562 cells in the presence of interleukin (IL)-2, IL-15, and IL-21 for 21 days. As a result, we found that expression markers of activated NK cells such as NKp30, NKp44, NKp46, NKG2D, CD244, perforin, granzyme B, and tumor necrosis factor alpha were highly upregulated. In addition, we found there was upregulated production of interferon gamma of activated NK cells against target cells such as REM134 and CF41.Mg. Specifically, we observed that cytotoxicity of NK cells against target cells was more sensitively reacted to CF41.Mg than REM134. Based on the results of this study, we recommend the development of an experimental application of CF41Mg, which has not been reported in canine mammary carcinoma research.

Keywords

References

  1. Korean Breast Cancer Society. Breast Cancer Facts & Figures 2018. Korean Breast Cancer Society, Seoul, 2018.
  2. Baioni E, Scanziani E, Vincenti MC, Leschiera M, Bozzetta E, Pezzolato M, Desiato R, Bertolini S, Maurella C, Ru G. Estimating canine cancer incidence: findings from a populationbased tumour registry in northwestern Italy. BMC Vet Res 2017;13:203. https://doi.org/10.1186/s12917-017-1126-0
  3. Moulton JE, Rosenblatt LS, Goldman M. Mammary tumors in a colony of beagle dogs. Vet Pathol 1986;23:741-749. https://doi.org/10.1177/030098588602300613
  4. Park JS, Withers SS, Modiano JF, Kent MS, Chen M, Luna JI, Culp WT, Sparger EE, Rebhun RB, Monjazeb AM, Murphy WJ, Canter RJ. Canine cancer immunotherapy studies: linking mouse and human. J Immunother Cancer 2016;4:97. https://doi.org/10.1186/s40425-016-0200-7
  5. Innes JR, Parry HB, Berger J. Leukaemia in dogs; including a record of a case treated by urethane. Br Vet J 1946;102:383-393.
  6. Brick JO, Roenigk WJ, Wilson GP. Chemotherapy of malignant lymphoma in dogs and cats. J Am Vet Med Assoc 1968;153:47-52.
  7. Addissie S, Klingemann H. Cellular immunotherapy of canine cancer. Vet Sci 2018;5:100. https://doi.org/10.3390/vetsci5040100
  8. Suen WC, Lee WY, Leung KT, Pan XH, Li G. Natural killer cell-based cancer immunotherapy: a review on 10 years completed clinical trials. Cancer Invest 2018;36:431-457. https://doi.org/10.1080/07357907.2018.1515315
  9. Canter RJ, Grossenbacher SK, Foltz JA, Sturgill IR, Park JS, Luna JI, Kent MS, Culp WT, Chen M, Modiano JF, Monjazeb AM, Lee DA, Murphy WJ. Radiotherapy enhances natural killer cell cytotoxicity and localization in pre-clinical canine sarcomas and first-in-dog clinical trial. J Immunother Cancer 2017;5:98. https://doi.org/10.1186/s40425-017-0305-7
  10. Levitz SM, Dupont MP, Smail EH. Direct activity of human T lymphocytes and natural killer cells against Cryptococcus neoformans. Infect Immun 1994;62:194-202. https://doi.org/10.1128/iai.62.1.194-202.1994
  11. Huang YC, Hung SW, Jan TR, Liao KW, Cheng CH, Wang YS, Chu RM. CD5-low expression lymphocytes in canine peripheral blood show characteristics of natural killer cells. J Leukoc Biol 2008;84:1501-1510. https://doi.org/10.1189/jlb.0408255
  12. Kaszak I, Ruszczak A, Kanafa S, Kacprzak K, Krol M, Jurka P. Current biomarkers of canine mammary tumors. Acta Vet Scand 2018;60:66. https://doi.org/10.1186/s13028-018-0417-1
  13. Goossens N, Nakagawa S, Sun X, Hoshida Y. Cancer biomarker discovery and validation. Transl Cancer Res 2015;4:256-269.
  14. Michishita M, Akiyoshi R, Yoshimura H, Katsumoto T, Ichikawa H, Ohkusu-Tsukada K, Nakagawa T, Sasaki N, Takahashi K. Characterization of spheres derived from canine mammary gland adenocarcinoma cell lines. Res Vet Sci 2011; 91:254-260. https://doi.org/10.1016/j.rvsc.2010.11.016
  15. Queiroga FL, Raposo T, Carvalho MI, Prada J, Pires I. Canine mammary tumours as a model to study human breast cancer: most recent findings. In Vivo 2011;25:455-465.
  16. Selman PJ, Mol JA, Rutteman GR, van Garderen E, Rijnberk A. Progestin-induced growth hormone excess in the dog originates in the mammary gland. Endocrinology 1994;134:287-292. https://doi.org/10.1210/en.134.1.287
  17. Fanelli MA, Vargas-Roig LM, Gago FE, Tello O, Lucero De Angelis R, Ciocca DR. Estrogen receptors, progesterone receptors, and cell proliferation in human breast cancer. Breast Cancer Res Treat 1996;37:217-228. https://doi.org/10.1007/bf01806503
  18. Pang LY, Argyle DJ. Using naturally occurring tumours in dogs and cats to study telomerase and cancer stem cell biology. Biochim Biophys Acta 2009;1792:380-391. https://doi.org/10.1016/j.bbadis.2009.02.010
  19. Tume L, Paco K, Ubidia-Incio R, Moya J. CD133 in breast cancer cells and in breast cancer stem cells as another target for immunotherapy. Gac Mex Oncol 2016;15:22-30. https://doi.org/10.1016/j.gamo.2016.01.003
  20. Jacobs JJ, Scheijen B, Voncken JW, Kieboom K, Berns A, van Lohuizen M. Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARF. Genes Dev 1999;13:2678-2690. https://doi.org/10.1101/gad.13.20.2678
  21. Nieman MT, Prudoff RS, Johnson KR, Wheelock MJ. Ncadherin promotes motility in human breast cancer cells regardless of their E-cadherin expression. J Cell Biol 1999;147:631-644. https://doi.org/10.1083/jcb.147.3.631
  22. Norval M, Maingay J, Else RW. Studies of three canine mammary cell lines--II. In vivo properties. Eur J Cancer Clin Oncol 1984;20:1501-1508. https://doi.org/10.1016/0277-5379(84)90143-3
  23. Leonel C, Borin TF, de Carvalho Ferreira L, Moschetta MG, Bajgelman MC, Viloria-Petit AM, de Campos Zuccari DA. Inhibition of epithelial-mesenchymal transition and metastasis by combined TGFbeta knockdown and metformin treatment in a canine mammary cancer xenograft model. J Mammary Gland Biol Neoplasia 2017;22:27-41. https://doi.org/10.1007/s10911-016-9370-7
  24. Jackisch C, Lammers P, Jacobs I. Evolving landscape of human epidermal growth factor receptor 2-positive breast cancer treatment and the future of biosimilars. Breast 2017;32:199-216. https://doi.org/10.1016/j.breast.2017.01.010
  25. Roman-Rosales AA, Garcia-Villa E, Herrera LA, Gariglio P, Diaz-Chavez J. Mutant p53 gain of function induces HER2 over-expression in cancer cells. BMC Cancer 2018;18:709. https://doi.org/10.1186/s12885-018-4613-1
  26. Ozaki T, Nakagawara A. Role of p53 in cell death and human cancers. Cancers (Basel) 2011;3:994-1013. https://doi.org/10.3390/cancers3010994
  27. Textor S, Fiegler N, Arnold A, Porgador A, Hofmann TG, Cerwenka A. Human NK cells are alerted to induction of p53 in cancer cells by upregulation of the NKG2D ligands ULBP1 and ULBP2. Cancer Res 2011;71:5998-6009. https://doi.org/10.1158/0008-5472.CAN-10-3211