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First published online November 17, 2005
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2005-0459v1
24/3/501    most recent
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Submitted on September 19, 2005
Accepted on November 13, 2005

Experimental Protocols for Embryonic Stem Cell Research

A 3-D Model to Study the Epigenetic Effects Induced by the Microenvironment of Human Embryonic Stem Cells

Lynne-Marie Postovit 1, Elisabeth A. Seftor 1, Richard E.B. Seftor 1, Mary J.C. Hendrix 1*

1 Children's Memorial Research Center, Cancer Biology and Epigenomics Program, Robert H. Lurie Comprehensive Cancer Center, Northwestern University's Feinberg School of Medicine, Chicago, Illinois

* To whom correspondence should be addressed. E-mail: mjchendrix{at}childrensmemorial.org.


  Abstract

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. As a corollary of these findings, we have developed a 3-D model that allows melanoma cells to be exposed to the microenvironment of human embryonic stem cells (hESCs). Utilizing 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 following culture on hESC microenvironments. These findings demonstrate the utility of this 3-D model to study the unique factors deposited by hESCs and to investigate the epigenetic effects that stem cell microenvironments may have on tumor progression.

Key Words. human embryonic stem cells, melanoma, microenvironment, conditioned matrix




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