개 유선종양세포에 대한 자연살해세포 독성 = Cytotoxicity of natural killer cells on canine mammary carcinoma cells

다국어 초록 (Multilingual 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.

참고문헌 (Reference)

1 Pang LY, "Using naturally occurring tumours in dogs and cats to study telomerase and cancer stem cell biology" 1792 : 380-391, 2009

2 Norval M, "Studies of three canine mammary cell lines--II. In vivo properties" 20 : 1501-1508, 1984

3 Ozaki T, "Role of p53 in cell death and human cancers" 3 : 994-1013, 2011

4 Canter RJ, "Radiotherapy enhances natural killer cell cytotoxicity and localization in pre-clinical canine sarcomas and first-in-dog clinical trial" 5 : 98-, 2017

5 Selman PJ, "Progestin-induced growth hormone excess in the dog originates in the mammary gland" 134 : 287-292, 1994

6 Nieman MT, "Ncadherin promotes motility in human breast cancer cells regardless of their E-cadherin expression" 147 : 631-644, 1999

7 Suen WC, "Natural killer cell-based cancer immunotherapy : a review on 10 years completed clinical trials" 36 : 431-457, 2018

8 Román-Rosales AA, "Mutant p53 gain of function induces HER2over-expression in cancer cells" 18 : 709-, 2018

9 Moulton JE, "Mammary tumors in a colony of beagle dogs" 23 : 741-749, 1986

10 Innes JR, "Leukaemia in dogs; including a record of a case treated by urethane" 102 : 383-393, 1946

11 Leonel C, "Inhibition of epithelial-mesenchymal transition and metastasis by combined TGFbeta knockdown and metformin treatment in a canine mammary cancer xenograft model" 22 : 27-41, 2017

12 Textor S, "Human NK cells are alerted to induction of p53 in cancer cells by upregulation of the NKG2D ligands ULBP1 and ULBP2" 71 : 5998-6009, 2011

13 Jackisch C, "Evolving landscape of human epidermal growth factor receptor 2-positive breast cancer treatment and the future of biosimilars" 32 : 199-216, 2017

14 Fanelli MA, "Estrogen receptors, progesterone receptors, and cell proliferation in human breast cancer" 37 : 217-228, 1996

15 Baioni E, "Estimating canine cancer incidence : findings from a populationbased tumour registry in northwestern Italy" 13 : 203-, 2017

16 Levitz SM, "Direct activity of human T lymphocytes and natural killer cells against Cryptococcus neoformans" 62 : 194-202, 1994

17 Kaszak I, "Current biomarkers of canine mammary tumors" 60 : 66-, 2018

18 Brick JO, "Chemotherapy of malignant lymphoma in dogs and cats" 153 : 47-52, 1968

19 Michishita M, "Characterization of spheres derived from canine mammary gland adenocarcinoma cell lines" 91 : 254-260, 2011

20 Addissie S, "Cellular immunotherapy of canine cancer" 5 : 100-, 2018

21 Queiroga FL, "Canine mammary tumours as a model to study human breast cancer : most recent findings" 25 : 455-465, 2011

22 Park JS, "Canine cancer immunotherapy studies : linking mouse and human" 4 : 97-, 2016

23 Goossens N, "Cancer biomarker discovery and validation" 4 : 256-269, 2015

24 Huang YC, "CD5-low expression lymphocytes in canine peripheral blood show characteristics of natural killer cells" 84 : 1501-1510, 2008

25 Tume L, "CD133 in breast cancer cells and in breast cancer stem cells as another target for immunotherapy" 15 : 22-30, 2016

26 Korean Breast Cancer Society, "Breast Cancer Facts & Figures 2018"

27 Jacobs JJ, "Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARF" 13 : 2678-2690, 1999