Postovit Lynne-Marie, Seftor Elisabeth A, Seftor Richard E B, Hendrix Mary J C
Children's Memorial Research Center, Chicago, Illinois 60614, USA.
Stem Cells. 2006 Mar;24(3):501-5. doi: 10.1634/stemcells.2005-0459. Epub 2005 Nov 17.
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.
需要新的研究方法来确定调节干细胞特性的稳态机制，并确定干细胞微环境对肿瘤细胞表型可能产生的表观遗传影响。我们最近证明，斑马鱼胚胎微环境可以消除侵袭性皮肤黑色素瘤细胞的致瘤性。作为这些发现的推论，我们开发了一种三维（3D）模型，该模型允许黑色素瘤细胞暴露于人类胚胎干细胞（hESCs）的微环境中。使用这种方法，我们确定hESC微环境可以显著影响侵袭性黑色素瘤细胞的行为。具体而言，将肿瘤细胞暴露于H1或HSF-6-hESC基质中会诱导出类似黑素细胞的表型，使其具有形成类似于hESCs的集落的能力。此外，黑色素瘤细胞在hESC微环境中培养后侵袭性降低。这些发现证明了这种3D模型在研究hESCs沉积的独特因素以及研究干细胞微环境可能对肿瘤进展产生的表观遗传效应方面的实用性。
