1 research outputs found
Restriction of Cancer Metastatic Potential Using Embryonic Stem Cells Encapsulated in Alginate Hydrogel Microstrands
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