The tumour microenvironment modulates cancer cell intravasation

Abstract

Development of three dimensional (3D) in vitro models to realistically recapitulate tumor microenvironment has the potential to improve translatability of anti-cancer drugs at the preclinical stage. To capture the in vivo complexity, these in vitro models should minimally incorporate the 3D interactions between multiple cell types, cellular structures such as vasculature and extracellular matrices. Here, we utilised microfluidic platforms to study the effect of various natural hydrogels (fibrin, collagen, Matrigel) and presence of tumor spheroids on the 3D vascularisation morphology. Various extracellular matrix (ECM) compositions impacted the vessel morphology while near the tumor spheroids the vessel diameter was considerably smaller for all different ECM compositions. Strikingly, cancer cells could enter the microvessel lumens (i.e. intravasate) only when the ECM was comprised of all the three types of hydrogels which increased the physical contact between the microvessels and the tumour spheroids. Our findings highlight the role of ECM composition in modulating the intravasation capacity of tumours.