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 utilized microfluidic platforms to study the effect of various natural hydrogels (fibrin, collagen, Matrigel) and presence of tumor spheroids on the 3D vascularisation morphology. Various 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 (intravasation) 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 tumors. • A human in vitro microfluidics model for visualising cancer cell intravasation was developed. • Composite hydrogel matrices emulate in vivo like complexities of the acellular tumour microenvironment. • Three-dimensional multicellular culture system recreates the complex tumour-stromal-vascular interactions. • Combination of collagen, Matrigel and fibrin hydrogels increased physical cellular interactions and enhanced cellular cross-talk.