Maria Isabel Carvalho1,2,3, Rodolfo Bianchini3, Judit Fazekas-Singer3,4, Ina Herrmann5, Irene Flickinger6, Johann G Thalhammer5, Isabel Pires1,2, Erika Jensen-Jarolim3,4, Felisbina L Queiroga7,8,9. 1. Animal and Veterinary Research Centre, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal. 2. Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal. 3. The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria. 4. Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, Austria. 5. Division of Dermatology, Internal Medicine Small Animals, University Clinics of Horses and Small Animals, University of Veterinary Medicine, Vienna, Austria. 6. Division of Oncology, Small Animal Internal Medicine, University Clinics of Horses and Small Animals, University of Veterinary Medicine, Vienna, Austria. 7. Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal fqueirog@utad.pt. 8. Center for the Study of Animal Sciences, Institute of Sciences, Technologies and Agro-environment, University of Porto, Porto, Portugal. 9. Center for Research and Technology of Agro-Environment and Biological Sciences, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal.
Abstract
BACKGROUND/AIM: Our aim was to investigate the crosstalk between tumor and immune cells (M2 macrophages) and its effects on cyclo-oxygenase-2 (COX2) regulation in canine mammary tumors (CMT). MATERIALS AND METHODS: Sh1b CMT cells and human BT474 mammary or HT29 colon cancer cells were co-cultured with canine peripheral blood mononuclear cells (PBMCs) or with macrophage-like differentiated THP1 monocytes (dTHP1). Intracellular COX2 expression by PBMCs, dTHP1 and cancer cells was evaluated by flow cytometry. RESULTS: Co-culturing of Sh1b and canine PBMCs induced COX2 overexpression in CMT cells. In turn, COX2 expression by PBMCs, mostly CD68+ macrophages, was attenuated by co-culture with Sh1b (p=0.0001). In accordance, co-culture with dTHP1 prompted intracellular production of COX2 in both Sh1b CMT cells and HT29 human colon cancer cells and reduced production of COX2 in BT474 human mammary cancer cells. The intracellular COX2 expression from dTHP1 decreased when treated with conditioned medium from cultured Sh1b and HT29 cancer cells. CONCLUSION: Bidirectional COX2 regulation between cancer and monocytes/macrophages might shape a tolerogenic tumor microenvironment in CMT. Copyright
BACKGROUND/AIM: Our aim was to investigate the crosstalk between tumor and immune cells (M2 macrophages) and its effects on cyclo-oxygenase-2 (COX2) regulation in canine mammary tumors (CMT). MATERIALS AND METHODS: Sh1b CMT cells and humanBT474 mammary or HT29 colon cancer cells were co-cultured with canine peripheral blood mononuclear cells (PBMCs) or with macrophage-like differentiated THP1 monocytes (dTHP1). Intracellular COX2 expression by PBMCs, dTHP1 and cancer cells was evaluated by flow cytometry. RESULTS: Co-culturing of Sh1b and canine PBMCs induced COX2 overexpression in CMT cells. In turn, COX2 expression by PBMCs, mostly CD68+ macrophages, was attenuated by co-culture with Sh1b (p=0.0001). In accordance, co-culture with dTHP1 prompted intracellular production of COX2 in both Sh1b CMT cells and HT29 humancolon cancer cells and reduced production of COX2 in BT474human mammary cancer cells. The intracellular COX2 expression from dTHP1 decreased when treated with conditioned medium from cultured Sh1b and HT29 cancer cells. CONCLUSION: Bidirectional COX2 regulation between cancer and monocytes/macrophages might shape a tolerogenic tumor microenvironment in CMT. Copyright
Authors: Xi He; Sarah E Smith; Shiyuan Chen; Hua Li; Di Wu; Paloma I Meneses-Giles; Yongfu Wang; Mark Hembree; Kexi Yi; Xia Zhao; Fengli Guo; Jay R Unruh; Lucinda E Maddera; Zulin Yu; Allison Scott; Anoja Perera; Yan Wang; Chongbei Zhao; KyeongMin Bae; Andrew Box; Jeffrey S Haug; Fang Tao; Deqing Hu; Darrick M Hansen; Pengxu Qian; Subhrajit Saha; Dan Dixon; Shrikant Anant; Da Zhang; Edward H Lin; Weijing Sun; Leanne M Wiedemann; Linheng Li Journal: Cell Rep Date: 2021-09-07 Impact factor: 9.423