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.

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.

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