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.
Highlights
Cancer remains a great social and economic burden in the Western world
In order to assess possible differences of oseltamivir phosphate treatment in benign and malignant cell lines, two mammary cell lines were used in this study: one adenoma-derived cell line (CMA07—established at our laboratory from a spontaneously occurring canine complex adenoma excised from a 6 year-old female dog for curative purposes with owners consent [31]) and one carcinoma-derived cell line (CMT-U27 – highly metastatic canine carcinoma cell line, kindly provided by Professor Eva Héllmen, from Sweden [32])
No statistically significant alterations were observed with 0.305 μM (p = 0.9781), 3.05 μM (p = 0.7436) and 30.5 μM (p = 0.9623) of oseltamivir phosphate treatments when compared with control cells (Fig 2B)
Summary
Cancer remains a great social and economic burden in the Western world. Despite all efforts to reduce such affliction, the number of patients has been increasing exponentially in the past few years. Breast cancer in particular is the most common cancer in women and the PLOS ONE | DOI:10.1371/journal.pone.0121590. Oseltamivir Phosphate Increases Canine Mammary Cancer Aggressiveness.
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