Anti-influenza inhibitor favours tumour aggressiveness in a canine model of breast cancer

Authors and Affiliations:

Joana T. de Oliveira¹,^2,3,4, Ana L. Santos¹,², Catarina Gomes¹,², Rita Barros¹,², Cláudia Ribeiro¹,², Nuno Mendes¹,², Augusto J. de Matos³,⁵, M. Helena Vasconcelos¹,^2,6, Maria José Oliveira¹,^7,8, Celso A. Reis¹,^2,3,8, Fátima Gärtner¹,^2,3

¹ Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal,

² Institute of Molecular Pathology and Immunology (IPATIMUP), University of Porto, Porto, Portugal,

³ Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), University of Porto, Porto, Portugal,

⁴ Faculty of Veterinary Medicine, Lusophone University of Humanities and Technologies, Lisbon, Portugal,

⁵ Animal Science and Study Central (CECA), Food and Agrarian Sciences and Technologies Institute (ICETA), Porto, Portugal,

⁶ Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal,

⁷ Institute of Biomedical Engineering (INEB), University of Porto, Porto, Portugal,

⁸ Department of Pathology and Oncology, Faculty of Medicine of the University of Porto, Porto, Portugal.

Abstract:

Oseltamivir phosphate is a widely used anti-influenza sialidase inhibitor. Sialylation, governed by sialyltransferases and sialidases, is strongly implicated in the oncogenesis and progression of breast cancer. In this study we evaluated the biological behavior of canine mammary tumor cells upon oseltamivir phosphate treatment (a sialidase inhibitor) in vitro and in vivo. Our in vitro results showed that oseltamivir phosphate impairs sialidase activity leading to increased sialylation in CMA07 and CMT-U27 canine mammary cancer cells. Surprisingly, oseltamivir phosphate stimulated, CMT-U27 cell migration and invasion capacity in vitro, in a dose-dependent manner. CMT-U27 tumors xenograft of oseltamivir phosphate-treated nude mice showed increased sialylation, namely α2,6 terminal structures and SLe(x) expression. Remarkably, a trend towards increased lung metastases was observed in oseltamivir phosphate-treated nude mice. Taken together, our findings revealed that oseltamivir impairs canine mammary cancer cell sialidase activity, altering the sialylation pattern of canine mammary tumors, and leading, surprisingly, to in vitro and in vivo increased mammary tumor aggressiveness.

Journal: PLOS ONE

Link: http://www.plosone.org/article/related/info:doi/10.1371/journal.pone.0121590