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Alginate Microcapsule as a 3D Platform for Propagation and Differentiation of Human Embryonic Stem Cells hESC to Different Lineages
Published on: March 9, 2012
Restriction of Cancer Metastatic Potential Using Embryonic Stem Cells Encapsulated in Alginate Hydrogel Microstrands
Bridget Mooney1, Nurazhani Abdul-Raof1, Yangzi Isabel Tian1
1Nanobioscience, Colleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, 257 Fuller Road, Albany, New York 12203, United States.
Abstract:
Current treatments focused on eradicating metastatic tumors have proven unsuccessful due to cancer's ability to quickly undergo epithelial-to-mesenchymal transition (EMT) and metastasize to secondary sites. Using human triple negative breast cancer cells (BCCs) as a model system, this work establishes a platform for the study of aggressive cancer phenotypes by demonstrating the inhibition of human metastatic cancer cells with 3D cultured embryonic stem cells (ESCs) encapsulated in alginate microstrands (ESC-microstrands), which mimic the embryonic microenvironment and recapitulate pluripotent signaling. Coculture with ESC-microstrands significantly decreases triple negative BCC proliferation and survival and reverses abnormal cancer metabolism. In particular, coculture with ESC-microstrands markedly restricts the metastatic potential of highly aggressive cancer cells, demonstrated as decreased migration and invasion, and reversed EMT marker expression. This indicates that pluripotent signaling from 3D ESC-microstrands could restrict cancer metastasis through restriction and reversion of EMT. Furthermore, two soluble factors associated with dysregulated oncogenic signaling were identified which display altered relative mRNA expression following coculture with ESC-microstrands. Future application of this model to mechanistic studies will enable a better understanding of cancer metastasis and the discovery of therapeutic targets for metastatic diseases.
Insights
Embryonic stem cells in 3D microstrands inhibit aggressive breast cancer metastasis by reversing epithelial-to-mesenchymal transition (EMT). This novel platform offers insights into cancer progression and potential therapeutic targets for metastatic disease.
Area of Science:
- Cancer Biology
- Stem Cell Biology
- Biotechnology
Background:
- Metastatic tumors are difficult to treat due to cancer cells undergoing epithelial-to-mesenchymal transition (EMT).
- Current treatments fail to effectively eradicate metastatic cancer, highlighting the need for new therapeutic strategies.
- Triple-negative breast cancer (BCC) serves as a model for aggressive cancer phenotypes.
Purpose of the Study:
- To establish a platform for studying aggressive cancer phenotypes using 3D cultured embryonic stem cells (ESCs).
- To investigate the inhibitory effects of ESC-microstrands on the metastatic potential of triple-negative BCCs.
- To identify soluble factors involved in oncogenic signaling that are affected by ESC-microstrand coculture.
Main Methods:
- Human triple-negative BCCs were cocultured with 3D cultured ESCs encapsulated in alginate microstrands (ESC-microstrands).
- The platform mimicked the embryonic microenvironment and recapitulated pluripotent signaling.
- Cancer cell proliferation, survival, metabolism, migration, invasion, and EMT marker expression were analyzed.
Main Results:
- Coculture with ESC-microstrands significantly decreased triple-negative BCC proliferation and survival.
- Metastatic potential was markedly restricted, evidenced by decreased migration and invasion.
- EMT marker expression was reversed, indicating a reversion of the metastatic phenotype.
- Two soluble factors associated with dysregulated oncogenic signaling showed altered mRNA expression.
Conclusions:
- Pluripotent signaling from 3D ESC-microstrands can restrict cancer metastasis by inhibiting and reverting EMT.
- This ESC-microstrand platform provides a novel model for studying cancer metastasis.
- The findings suggest potential therapeutic targets for metastatic diseases.

