Modelling the brain tumour microenvironment in 3D using tailored hydrogels

The matrix surrounding cancer cells plays a significant role in disease progression, with reciprocal signalling enabling cells to 'read' messages from the matrix and for tumour cells to re-engineer their matrix environment. Current models use animals or commercial matrix preparations in 2D culture in the lab. Neither option accurately replicates the complex protein and sugar compositions of human matrix.

Recently, we developed a fully synthetic, highly reproducible hydrogel based on a simple short peptide motif. Cancer cells, along with other cell types, can be encapsulated in the gels and easily grown in the lab. These gels can be easily functionalized with relevant proteins/peptides or glycans to create bespoke matrix environments, to mimic the tissues in which tumours develop.

There are at least 50 distinct types of primary brain tumours. With some tumour types only occurring in a very specific part of the brain at a defined developmental stage suggesting a permissive microenvironment briefly exists. In addition to this, only some types of primary tumours e.g. lung metastasize to the brain.

We will create bespoke matrix environments to test this hypothesis and identify the key factors/cellular interactions that limit or indeed promote tumour growth and progression.