Oncological model systems and High Content Imaging

In vitro models are intended to allow researchers to recapitulate aspects of the tumor microenvironment using specific cell types, extracellular matrices, and soluble factors. Traditionally, 2D cell culture of cancer cell lines have been used in high content imaging to identify potential new anti-cancer treatments or identify aberrant phenotypes arising from cancer-related genetic mutations. Such immortalized cell lines, such as the HeLa cells, have provided important insights into oncological cell biology.  Recent studies, however, are discovering that the hard, unnatural substrate the cells are grown upon can influence their behavior, giving rise to poor predictions of biological function or compound response in tissues or animal models.

Up to now, moving away from 2D cell culture meant implanting tumor samples into mice.  Now, innovative 3D cell culture techniques, such as spheroids and organoids, are bridging the gap between cell in vitro culture and in vivo experiments to study tumor cell behaviour.  These methods mimic the 3D physiology within our body to allow for more natural intercellular contacts and inclusion of mechanical effects and chemical signalling into the overarching experimental design.

As well, Zebrafish (Danio rerio) are an emerging animal model for in-vivo cancer studies.  The fish are an attractive animal model because of their fast growth with cost-effective maintenance and the possibility of chemical screening in large numbers of animals at reasonable costs.  Too, they benefit from amenability to microscopy for easy, direct visualization of implanted human tumor xenografts within the fish for simultaneous evaluation of cell behavior and compound toxicology[1].

High content imaging allows the automated imaging and analysis of all the above mentioned models in one single platform. A wide range of magnifications and fluorescence wavelengths, alongside Z-stack and de-convolution image processing tools, enable flexibility and versatility to support a broad range of experimental designs.  Biology can be studied from the sub-cellular range of a few hundreds of nanometres, up to three dimensional structures and whole organisms on the scale of a few millimetres.  Furthermore, such sophisticated screening systems have the ability to track and study rare events occurring in only a few cells within a population, a feature particularly suited for studies on diseases like cancer.