Abstract
Metastasis underlies the majority of cancer-related deaths yet remains poorly understood due, in part, to the lack of models in vivo. Here we show that expression of the EMT master inducer Snail in primary adult Drosophila intestinal tumors leads to the dissemination of tumor cells and formation of macrometastases. Snail drives an EMT in tumor cells, which, although retaining some epithelial markers, subsequently break through the basal lamina of the midgut, undergo a collective migration and seed polyclonal metastases. While metastases re-epithelialize over time, we found that early metastases are remarkably mesenchymal, discarding the requirement for a mesenchymal-to-epithelial transition for early stages of metastatic growth. Our results demonstrate the formation of metastases in adult flies, and identify a key role for partial-EMTs in driving it. This model opens the door to investigate the basic mechanisms underlying metastasis, in a powerful in vivo system suited for rapid genetic and drug screens.
Highlights
Metastasis underlies the majority of cancer-related deaths yet remains poorly understood due, in part, to the lack of models in vivo
We find that expression of Snail (Sna) in adult Drosophila intestinal Apc-Ras tumors leads to the formation of macrometastases, which shows remarkable parallels to human metastases
While flies and fish have emerged as powerful tools to investigate malignancy and perform largescale genetic and drug screens, to date studies have been limited by a lack of metastatic models where cells can be followed from primary tumor development to growth of macrometastases in adult organisms
Summary
Metastasis underlies the majority of cancer-related deaths yet remains poorly understood due, in part, to the lack of models in vivo. While flies and fish have emerged as powerful tools to investigate malignancy and perform largescale genetic and drug screens, to date studies have been limited by a lack of metastatic models where cells can be followed from primary tumor development to growth of macrometastases in adult organisms. We overcome this issue as we have developed highly sensitive assays that enable the detection of circulating tumor cells, which, combined with in vivo imaging, makes all steps of the process accessible to analysis
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