Continuous high-resolution in vivo imaging reveals tumor-specific dissemination in an embryonic zebrafish xenograft model

Abstract

Mechanisms mediating tumor metastasis are crucial for diagnostic and therapeutic targeting. Here, we take advantage of a transparent embryonic zebrafish xenograft model (eZXM) to visualize and track injected human leukemic and breast cancer cells in real time using selective plane illumination microscopy (SPIM) for up to 30 hours. Injected cells exhibited disease-specific patterns of intravascular distribution with leukemic cells moving faster than breast cancer cells. While breast cancer cells predominantly adhered to nearby regions, about 30% invaded the avascularized tissue, reminiscent of their metastatic phenotype. Survival of the injected tumor cells was partly inhibited by the cellular innate immune system of the recipient embryos and leukemic cell dissemination was effectively inhibited by pharmacological ROCK1 blockade. These observations, and the ability to image several embryos simultaneously, support the use of eZXM and SPIM imaging as a functional screening platform to identify compounds that restricts cancer cell spread and invasion.