CYTOO S.A. announced new results that demonstrate the ability of the Company’s 2D+ Cell Culture Platform to reproduce in vivo conditions to analyze tumor cell motility and in particular to study fibrillar ECM-dependent tumor cell-macrophage pairing and migration involved in tumor metastasis. These results have recently been published in the first issue of the journal IntraVital, edited by Landes Bioscience.
The CYTOO 2D+ Cell Culture Platform is based on the use of adhesive micropatterns to guide cell architecture and behavior in culture, in contrast to current 2D cell culture where cells spread and move in an uncontrolled manner. By defining the 2D topology of cell adhesion, 2D+ Technology enables the fine control of the spreading and 3D shape of cultured cells in single- or multi-cellular configurations resulting in control of cell contractility, cell polarity, organelle positioning, or cell division axis.
Researchers Ved Sharma, Brian Beaty, Antonia Patsialou, Dianne Cox, John Condeelis and Robert Eddy from the Albert Einstein College of Medicine, NY, with collaborators Huiping Liu from University of Chicago and Michael Clarke at Stamford School of Medicine, used CYTOOchipsTM Motility to reconstitute an in vitro model of fibrillar tumor extracellular matrix (ECM). The micropatterned 1D adhesive tracks were used to mimic the linear ECM fibers of the tumor microenvironment.
Similar morphologies, behaviors and motility rates were observed in vivo and on micropatterned lines. In particular, tumor cell velocity on 1D substrates was in agreement with the high velocity values of tumor cells on ECM fibers observed in vivo. In contrast, on classical 2D substrates, motility rates were ten fold lower than what can be observed in vivo. On micropatterned lines, the authors could also reproduce the assembly of alternating tumor cells and macrophages identified as streams in vivo, the ability of macrophages to enhance protrusion velocity and average velocity of tumor cells and showed that this effect was dependent on an intact paracrine loop without any additional need of co-factors.
The authors concluded that their “1D micropatterned substrate model more closely approximates the fibrillar nature of the in vivo tumor microenvironment and offers a simple and more appropriate substrate for detailed analyses of cell protrusion, cell-cell pairing and migration than conventional 2D substrates. The data presented here validates the use of micropatterned 1D adhesive substrates to study the fibrillar ECM found within the tumor microenvironment.”
Co-author Robert Eddy commented “It was a surprise that tumor cell and macrophage streaming behavior we observe in the highly complex tumor microenvironment was self-organizing and required no other extracellular cues on 1D adhesive substrates.”