Live imaging the earliest host innate immune response to preneoplastic cells using a zebrafish inducible...

As cancers develop, transformed cells hijack various host mechanisms and manipulate them to create a dynamic tumor microenvironment, which supports tumor growth. This protumorigenic microenvironment is made up of many different cell types, including transformed cells, fibroblasts, inflammatory cells, and endothelial cells, the interactions of which have been shown to play a role in sustaining tumor growth. Multiple reports implicate the inflammatory cells of the tumor microenvironment as having both pro- and antitumorigenic roles, the balance of which is vital for the progression of the tumor, and while our understanding of established cancers has vastly increased since the turn of the 21st Century, our knowledge of these cellular interactions at the earliest stages of cancer initiation and development remains relatively limited. This is largely due to difficulties in monitoring these processes in vivo and in real time. Since the late nineties, the zebrafish (Danio rerio) has emerged as a vital model organism, allowing studies of previously unattainable stages of tumor initiation in a vertebrate model system. Using genetic and live-imaging approaches, this model system can be used both independently to monitor stages of tumor progression from the earliest initiation stages and incorporated into previously established systems to investigate the interactions between cancer cells and the various cell types of the tumor microenvironment, including inflammatory cells. Here, we describe the use of an inducible KalTA4-ER^T2/UAS expression system in zebrafish, which allows spatial and temporal control of preneoplastic cell (PNC) growth and monitoring of innate immune cells in response to the developing PNC microenvironment.