Affiliation:
1. Department of Applied Physics Aalto University P.O. Box 15100 Aalto Espoo FI‐00076 Finland
2. Department of Electrical Engineering and Automation Aalto University P.O. Box 12200 Aalto Espoo FI‐00076 Finland
3. Finnish Cancer Institute and FICAN South Helsinki University Hospital & Cancer Cell Circuitry Laboratory Translational Cancer Medicine Medical Faculty University of Helsinki P.O. Box 63 (Haartmaninkatu 8) Helsinki 00014 Finland
4. Faculty of Engineering and Natural Sciences Tampere University P.O. Box 541 Tampere FI‐33720 Finland
Abstract
AbstractThe extracellular matrix (ECM)‐regulated phenotypic plasticity is crucial for metastatic progression of triple negative breast cancer (TNBC). While ECM faithful cell‐based models are available for in situ and invasive tumors, such as cell aggregate cultures in reconstituted basement membrane and in collagenous gels, there are no ECM faithful models for metastatic circulating tumor cells (CTCs). Such models are essential to represent the stage of metastasis where clinical relevance and therapeutic opportunities are significant. Here, CTC‐like DU4475 TNBC cells are cultured in mechanically tunable 3D fibrin hydrogels. This is motivated, as in circulation fibrin aids CTC survival by forming a protective coating reducing shear stress and immune cell‐mediated cytotoxicity and promotes several stages of late metastatic processes at the interface between circulation and tissue. This work shows that fibrin hydrogels support DU4475 cell growth, resulting in spheroid formation. Furthermore, increasing fibrin stiffness from 57 to 175 Pa leads to highly motile, actin and tubulin containing cellular protrusions, which are associated with specific cell morphology and gene expression patterns that markedly differ from basement membrane or suspension cultures. Thus, mechanically tunable fibrin gels reveal specific matrix‐based regulation of TNBC cell phenotype and offer scaffolds for CTC‐like cells with better mechano‐biological properties than liquid.
Funder
Business Finland
Syöpäsäätiö
European Research Council
Academy of Finland
Subject
Pharmaceutical Science,Biomedical Engineering,Biomaterials