Leukotriene D4 Levels in Patıents With Breast Cancer

Year 2022, Volume: 47 Issue: 3, 331 - 338, 19.10.2022

Sevgi Akaydın , Sümeyye Ramazanoğlu Ece Miser Salihoğlu , Hasan Karanlık , Semra Demokan

https://doi.org/10.55262/fabadeczacilik.1086291

Abstract

Leukotriene D4 (LTD4) is an inflammatory mediator synthesized in the arachidonic acid pathway and has been reported to induce cell proliferation and survival in cancer. LTD4 is synthesized from LTC4 by the enzyme gamma-glutamyltransferase (GGT). Here, we examined serum LTD4 levels and the relationship of LTD4 with GGT in patients with breast cancer. For that purpose, serum samples were taken from 43 patients diagnosed with breast cancer and 8 healthy controls. The patients were divided into five subgroups, as Luminal A, Luminal B, Luminal B-HER2(+), HER2(+) and triple negative. LTD4 levels were measured by ELISA method. Mean levels of LTD4 in the patients were significantly higher than in healthy controls [3,43 (2,21) ng/mL vs 1,47 (0,46) ng/mL; p < 0.05]. According to the molecular subtypes, serum LTD4 levels were found to be significantly higher in the Luminal A, Luminal B and Triple (-) subgroups than in the controls (p <0.01, p <0.005 and p <0.005, respectively). Higher levels of LTD4 have been observed in post-menopausal patients than in pre-menopausal patients (p <0,05). A statistically significant positive correlation was observed between GGT activity and LTD4 levels in the whole study group and post-menopausal patients (R=0.349, p=0.014 and R=0.437, p=0.042, respectively). According to the literature, this study is the first to examine LTD4 levels in breast cancer and supports other studies showing the role of leukotrienes in cancer. Because of LTD4's ability to induce proliferation and inhibit apoptosis, increased levels of LTD4 in our study may be associated with cancer development, especially in post-menopausal women.

Keywords

Leukotriene D4, Gamma-Glutamyltransferase, Breast Cancer, Post-menopausal Status

Project Number

02/2017-02

References

• Almutlaq, B.A., Almuazzi, R.F., Almuhayfir, A.A., Alfouzan, A.M., Alshammari, B.T., AlAnzi, H.S., … Ahmed, H.G. (2017). Breast cancer in Saudi Arabia and its possible risk factors. Journal of Cancer Policy, 12,83-89. https://doi.org/10.1016/j.jcpo.2017.03.004.
• Bellamkonda, K., Chandrashekar, N. K., Osman, J., Selvanesan, B. C., Savari, S., Sjölander, A. (2016). The eicosanoids leukotriene D4 and prostaglandin E2 promote the tumorigenicity of colon cancer-initiating cells in a xenograft mouse model. BMC Cancer, 16(1), 1–14. https://doi.org/10.1186/s12885-016-2466-z.
• Bishayee, K., Khuda-Bukhsh, A.R. (2013).5-Lipoxygenase Antagonist therapy: a new approach towards targeted cancer chemotherapy. Acta Biochimica et Biophysica Sinica, 45(9), 709–719. https://doi.org/10.1093/abbs/gmt064.
• Corti, A., Franzini, M., Paolicchi, A., Pompella, A. (2010). Gamma-glutamyltransferase of cancer cells at the crossroads of tumor progression, drug resistance and drug targeting. Anticancer Research, 4, 1169-81.
• Funk, C. D. (2001). Prostaglandins and leukotrienes: Advances in eicosanoid biology. Science, 294(5548),1871-875. https://doi.org/10.1126/science.294.5548.1871.
• Goldhirsch, A., Wood, W.C., Coates, A.S., Gelber, R.D., Thürlimann, B., Senn, H.J. (2011) Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Annals of Oncology, 22(8),1736-47. https://doi.org/10.1093/annonc/mdr304.
• Hanigan M.H. (2014). Gamma-glutamyl transpeptidase: redox regulation and drug resistance. Advances in Cancer Research, 122, 103–141. https://doi.org/10.1016/B978-0-12-420117-0.00003-7.
• Harris, R.E., Chlebowski, R.T., Jackson, R.D., Frid, D.J., Ascenseo, J.L., Anderson, G., Loar, A., ….Women's Health Initiative (2003). Breast cancer and nonsteroidal anti-inflammatory drugs: prospective results from the Women's Health Initiative. Cancer research, 63(18), 6096–6101.
• Korniluk, A., Koper, O., Kemona, H., Dymicka-Piekarska, V. (2017). From inflammation to cancer, Irish Journal of Medical Science, 186 (1), 57–62. https://doi.org/10.1007/s11845-016-1464-0.
• Lukic, A., Ji, J., Idborg, H., Samuelsson, B., Palmberg, L., Gabrielsson, S., … Rådmark, O. (2016). Pulmonary epithelial cancer cells and their exosomes metabolize myeloid cell-derived leukotriene C4 to leukotriene D4. Journal of lipid research, 57(9), 1659–1669. https://doi.org/10.1194/jlr.M066910.
• Madeddu, C., Gramignano, G., Floris, C., Murenu, G., Sollai, G., Macciò, A. (2014). Role of inflammation and oxidative stress in post-menopausal oestrogen-dependent breast cancer. Journal of cellular and molecular medicine, 18(12), 2519–2529. https://doi.org/10.1111/jcmm.12413.
• Magnusson, C., Liu, J., Ehrnström, R., Manjer, J., Jirström, K., Andersson, T.,… Sjölander, A. (2011). Cysteinyl leukotriene receptor expression pattern affects migration of breast cancer cells and survival of breast cancer patients. International Journal of Cancer, 129(1), 9-22. https://doi.org/10.1002/ijc.25648.
• Ohd, J.F., Nielsen, C.K., Campbell, J., Landberg, G., Löfberg, H., Sjölander, A. (2003). Expression of the leukotriene D4 receptor CysLT1, COX-2, and other cell survival factors in colorectal adenocarcinomas. Gastroenterology, 124(1),57-70. https://doi.org/ 10.1053/gast.2003.50011.
• Paruchuri, S., Sjölander, A. (2003). Leukotriene D4 Mediates Survival and Proliferation via Separate but Parallel Pathways in the Human Intestinal Epithelial Cell Line Int 407. J. Biol. Chem., 278 (46), 45577–45585. https://doi.org/10.1074/jbc.M302881200.
• Paruchuri, S., Broom, O., Dib, K., Sjölander, A. (2005). The pro-inflammatory mediator leukotriene D4 induces phosphatidylinositol 3-kinase and Rac-dependent migration of intestinal epithelial cells. The Journal of Biological Chemistry, 280(14), 13538–13544. https://doi.org/10.1074/jbc.M409811200.
• Peters-Golden, M., Henderson, W. R. (2007). Leukotrienes. New England Journal of Medicine, (357),1841-1854. https://doi.org/10.1056/NEJMra071371.
• Przylipiak, A., Hafner, J., Przylipiak, J., Köhn, F. M., Runnebaum, B., Rabe, T. (1998). Influence of 5-lipoxygenase on in vitro growth of human mammary carcinoma cell line MCF-7. Gynecologic and obstetric investigation, 46(1), 61–64. https://doi.org/10.1159/000010000.
• Salim, T., Sand-Dejmek, J., Sjölander, A. (2014). The inflammatory mediator leukotriene D4 induces subcellular β-catenin translocation and migration of colon cancer cells. Experimental Cell Research, 321(2), 255-266. https://doi.org/10.1016/j.yexcr.2013.10.021.
• Shi, Z-Z., Han, B., Habib, G.M., Matzuk, M. M., Lieberman, M.W. (2001). Disruption of γ-glutamyl leukotrienase results in disruption of leukotriene D4 synthesis in vivo and attenuation of the acute inflammatory response. Molecular and Cellular Biology, 21(16), 5389-5395. https://doi.org/10.1128/MCB.21.16.5389-5395.2001.
• Shimakura, S., Boland, C.R. (1992). Eicosanoid production by the human gastric cancer cell line AGS and its relation to cell growth. Cancer research, 52(7), 1744–1749.
• Todoric, J., Antonucci, L., Karin, M. (2016). Targeting inflammation in cancer prevention and therapy. Cancer Prevention Research, 9 (12), 895–905. https://doi.org/10.1158/1940-6207.CAPR-16-0209.
• Tsai, M.J., Chang, W.A., Chuang, C.H., Wu, K.L., Cheng, C.H., Sheu, C.C., … Hung, J.Y. (2021). Cysteinyl Leukotriene Pathway and Cancer. International Journal of Molecular Sciences, 23(1), 120. https://doi.org/10.3390/ijms23010120.
• Verma, V.V., Gupta, R., Goel, M. (2015). Phylogenetic and evolutionary analysis of functional divergence among Gamma glutamyl transpeptidase (GGT) subfamilies. Biology Direct (10)1, 1–21. https://doi.org/10.1186/s13062-015-0080-7.