Mesenchymal stem cells (MSCs) or fibroblasts are one of the most abundant cell types
in the tumor microenvironment (TME) exerting various anti- and pro-apoptotic effects
during tumorigenesis, invasion, and drug treatment. Despite the recently discovered
importance of MSCs in tumor progression and therapy, the response of these cells to
chemotherapeutics compared to cancer cells is rarely investigated. A widely accepted
view is that these naive MSCs have higher drug tolerance than cancer cells due to
a significantly lower proliferation rate. Here, we examine the differences and similarities
in the sensitivity of MSCs and cancer cells to nine diverse chemotherapy agents and
show that, although MSCs have a slower cell cycle, these cells are still sensitive
to various drugs. Surprisingly, MSCs showed similar sensitivity to a panel of compounds,
however, suffered fewer DNA double-stranded breaks, did not enter into a senescent
state, and was virtually incapable of apoptosis. Our results suggest that MSCs and
cancer cells have different cell fates after drug treatment, and this could influence
therapy outcome. These findings could help design drug combinations targeting both
MSCs and cancer cells in the TME.
