Engineering approaches to studying cancer cell migration in three-dimensional environments.

Cancer is one of the most devastating diseases of our time, with 17 million new cancer cases and 9.5 million cancer deaths in 2018 worldwide. The mortality associated with cancer results primarily from metastasis, i.e. the spreading of cancer cells from the primary tumour to other organs. The invasion and migration of cells through basement membranes, tight interstitial spaces and endothelial cell layers are key steps in the metastatic cascade. Recent studies demonstrated that cell migration through three-dimensional environments that mimic the in vivo conditions significantly differs from their migration on two-dimensional surfaces. Here, we review recent technological advances made in the field of cancer research that provide more 'true to the source' experimental platforms and measurements for the study of cancer cell invasion and migration in three-dimensional environments. These include microfabrication, three-dimensional bioprinting and intravital imaging tools, along with force and stiffness measurements of cells and their environments. These techniques will enable new studies that better reflect the physiological environment found in vivo, thereby producing more robust results. The knowledge achieved through these studies will aid in the development of new treatment options with the potential to ultimately lighten the devastating cost cancer inflicts on patients and their families. This article is part of a discussion meeting issue 'Forces in cancer: interdisciplinary approaches in tumour mechanobiology'.