Long-term dexamethasone treatment increases the engraftment efficiency of human breast cancer cells in adult zebrafish

Juliana Moreira Mendonça-Gomes; Thalita Marcolan Valverde; Thaís Maria da Mata Martins; Ives Charlie-Silva; Barbara Nunes Padovani; Camila Morales Fénero; Eloisa Martins da Silva; Rosana Zacarias Domingues; Daniela Chemim Melo-Hoyos; José Dias Corrêa-Junior; Niels Olsen Saraiva Câmara; Alfredo Miranda Góes; Dawidson Assis Gomes

doi:10.1016/j.fsirep.2021.100007

Long-term dexamethasone treatment increases the engraftment efficiency of human breast cancer cells in adult zebrafish

Fish Shellfish Immunol Rep. 2021 Mar 9:2:100007. doi: 10.1016/j.fsirep.2021.100007. eCollection 2021 Dec.

Authors

Juliana Moreira Mendonça-Gomes¹, Thalita Marcolan Valverde^{1

2}, Thaís Maria da Mata Martins², Ives Charlie-Silva³, Barbara Nunes Padovani⁴, Camila Morales Fénero⁴, Eloisa Martins da Silva⁴, Rosana Zacarias Domingues⁵, Daniela Chemim Melo-Hoyos⁶, José Dias Corrêa-Junior², Niels Olsen Saraiva Câmara⁴, Alfredo Miranda Góes^{1

7}, Dawidson Assis Gomes¹

Affiliations

¹ Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte - MG 31270-901, Brazil.
² Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte - MG 31270-901, Brazil.
³ Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo - SP 05508-900, Brazil.
⁴ Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo - SP 05508-900, Brazil.
⁵ Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte - MG 31270-901, Brazil.
⁶ Departamento de Zootecnia, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte - MG 31270-901, Brazil.
⁷ Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte - MG 31270-901, Brazil.

Abstract

The host immune system tends to reject xenogenic-implanted cells making tumor development in adult host animal models difficult. Immune system suppression is used for successful xenotransplantation of human cancer cells in many animal models. The studies of cancer development processes in vivo offer opportunities to understand cancer biology and discover new therapeutic strategies. In this context, zebrafish is a model that has been widely applied in the study of human diseases, such as cancer. However, the long-term immunosuppression of these adult zebrafish is still under study as a xenograft animal model for human cancer. This work aimed to evaluate the effects of 21 days of (long-term) exposure of dexamethasone in zebrafish-transplanted with MGSO-3 cells, human breast tumor cell line. Our results show that the animals, while kept on dexamethasone treatment, remained with a 50% reduction in the number of peripheral lymphocytes. In vitro data demonstrated that up to 7 days of dexamethasone treatment did not alter the morphology, proliferation, or viability of MGSO-3 cells. The animals that received a prolonged dexamethasone treatment allowed the engraftment of tumor cells in 100% of the zebrafish tested. These animals also showed tumor progression over 21 days. The experimental group that received only previous exposure to dexamethasone had their tumors regressed after 14 days. In conclusion, the prolonged use of dexamethasone in zebrafish showed a potential strategy for in vivo monitoring of xenograft tumor growth for development studies, as well as in anticancer drug discovery.

Keywords: Breast cancer, Lymphocytes; Immunosuppression; Xenotransplant; Zebrafish.