Nemzeti Gyógyszerkutatási és Fejlesztési Laboratórium (PharmaLab)(RRF-2.3.1-21-2022-00015)
Funder: NRDIO
(2019-1.3.1-KK-2019-00007) Funder: NKFIH
Subjects:
Bioinformatics, e-Health, medical informatics
Biochemistry and molecular biology
Chemical sciences
Mesenchymal stem cells (MSCs) are an integral part of the tumor microenvironment (TME);
however, their role is somewhat controversial: conflicting reports suggest that, depending
on the stage of tumor development, MSCs can either support or suppress tumor growth
and spread. Additionally, the influence of MSCs on drug resistance is also ambiguous.
Previously, we showed that, despite MSCs proliferating significantly more slowly than
cancer cells, there are chemotherapeutic drugs which proved to be similarly toxic
to both cell types. Here we established 2D co-cultures and 3D co-culture spheroids
from different ratios of GFP-expressing, adipose tissue-derived MSCs and A431 epidermoid
carcinoma cells tagged with mCherry to investigate the effect of MSCs on cancer cell
growth, survival, and drug sensitivity. We examined the cytokine secretion profile
of mono- and co-cultures, explored the inner structure of the spheroids, applied MSC-(nutlin-3)
and cancer cell-targeting (cisplatin) treatments separately, monitored the response
with live-cell imaging and identified a new, double-fluorescent cell type emerging
from these cultures. In 2D co-cultures, no effect on proliferation or drug sensitivity
was observed, regardless of the changes in cytokine secretion induced by the co-culture.
Conversely, 3D spheroids developed a unique internal structure consisting of MSCs,
which significantly improved cancer cell survival and resilience to treatment, suggesting
that physical proximity and cell–cell connections are required for MSCs to considerably
affect nearby cancer cells. Our results shed light on MSC–cancer cell interactions
and could help design new, better treatment options for tumors.
