Bioengineering embryonic microenvironment for exploring stem cell-breast cancer cell interactions

Embryonic stem (ES) cells and breast cancer cells share similar signaling pathways that allow cells to proliferate and differentiate. However, signaling molecules in cancer cells are misexpressed. Cell microenvironments that consist of many factors such as soluble factors, extracellular matrices, and neighboring cells, play a pivotal role in determining cellular fate. The exposure of ES cell microenvironments to cancer cells may address the missing components in the tumor microenvironment, which could inhibit tumorigenesis or reprogram cancer cells into a less invasive phenotype. In this thesis, in vitro ES cell microenvironments have been engineered three-dimensionally via alginate hydrogel encapsulation and patterned precisely using laser direct-write. These in vitro bioengineered embryonic microenvironments provide promising strategies for engineering tissues and studying the stem cell fate decision in order to create suitable niches for understanding stem cell-cancer cell interactions. In particular, three-dimensional (3D) embryonic microenvironments have been utilized to investigate inhibitory effects of ES cells on metastatic breast cancer cells. Results obtained from this study have demonstrated the ability of bioengineered embryonic microenvironments to inhibit the growth and migration of highly invasive breast cancer cells through the reduction of oncogene expression. This bioengineering approach provides a unique opportunity for finding alternative plans to understand breast cancer metastasis, leading to restriction and prevention of metastasis.