Using Zebrafish Xenotransplantation To Study Ewing's Sarcoma And Investigate The Role Of Y-Box Binding Protein 1 In Metastasis

Abstract

The most unfavourable prognostic factor for Ewing’s sarcoma (ES) is the presence of metastases. To date, a viable cancer model for ES metastasis has not been developed. Models for ES are crucial to uncovering the key molecular mechanisms that are responsible for metastasis. Therefore, we developed a zebrafish xenotransplantation model to better visualize and manipulate ES behaviour in vivo. Human ES TC32 cells were fluorescently labeled with Cm-DiI, and microinjected into the yolk sac of two-day-old casper embryos. TC32 cells successfully engrafted, survived, proliferated and migrated over 144 hours post-injection (hpi). Y-box binding protein 1 (YB-1) is highly expressed in a variety of cancers and plays a key role in promoting breast cancer metastasis. In contrast to TC32 cells with regular levels of YB-1, xenografted YB-1 knockdown TC32 cells showed significantly reduced migration. These studies highlight the utility of the zebrafish xenograft model to elucidate the mechanisms underlying the metastatic behavior of ES and position this system as an in vivo tool for drug discovery to identify novel anti-proliferative and anti-metastatic agents to improve outcome in this disease.