A three-dimensional model to study the epigenetic effects induced by the microenvironment of human embryonic stem cells.

New methods of study are necessary to define the homeostatic mechanisms that regulate stem cell properties and to determine the possible epigenetic influence of the stem cell microenvironment on the phenotype of tumor cells. We recently demonstrated that the tumorgenicity of aggressive cutaneous melanoma cells can be abrogated by the zebrafish embryonic microenvironment. We have developed a three-dimensional (3D) model, as a corollary of these findings, that allows melanoma cells to be exposed to the microenvironment of human embryonic stem cells (hESCs). Using this methodology, we determined that hESC microenvironments can dramatically influence the behavior of aggressive melanoma cells. Specifically, exposure of tumor cells to H1- or HSF-6-hESC matrices induced a melanocyte-like phenotype with the ability to form colonies similar to hESCs. Furthermore, melanoma cells were less invasive after culture on hESC microenvironments. These findings demonstrate the utility of this 3D model for studying the unique factors deposited by hESCs and for investigating the epigenetic effects that stem cell microenvironments may have on tumor progression.