Microenvironmental Modulation of Decorin and Lumican in @entity2903 -Resistant @entity463 and XXXX Stem-Like Cells.

@entity368 @entity5 @entity2904 @entity30080 @entity521 @entity2903 @entity4149 @entity463
The presence of @entity5 stem cells (CSCs) or @entity5 -initiating cells can lead to @entity5 recurrence in a permissive cell-microenvironment interplay, promoting @entity463 ( @entity463 ) and @entity521 ( @entity521 ). Extracellular matrix (ECM) small @entity368 -rich proteoglycans (SLRPs) play multiple roles in tissue homeostasis by remodeling the extracellular matrix (ECM) components and modulating intracellular signaling pathways. Due to their pan-inhibitory properties against receptor @entity4149 kinases (RTKs), SLRPs are reported to exert anticancer effects in vitro and in vivo. However, their roles seem to be tissue-specific and they are also involved in @entity5 cell migration and drug resistance, paving the way to complex different scenarios. The aim of this study was to determine whether the SLRPs decorin (DCN) and lumican ( @entity30080 ) are recruited in cell plasticity and microenvironmental adaptation of differentiated @entity5 cells induced towards stem-like phenotype. Floating neurospheres were generated by applying CSC enrichment medium (neural stem cell serum-free medium, NSC SFM) to the established SF-268 and SK-N-SH @entity5 cell lines, cellular models of @entity463 and @entity521 , respectively. In both models, the time-dependent synergistic activation of DCN and @entity30080 was observed. The highest DCN and @entity30080 mRNA/protein expression was detected after cell exposure to NSC SFM for 8/12 days, considering these cells as SLRP-expressing (SLRP+) CSC-like. Ultrastructural imaging showed the cellular heterogeneity of both the @entity463 and @entity521 neurospheres and identified the inner living cells. Parental cell lines of both @entity463 and @entity521 grew only in soft agar + NSC SFM, whereas the secondary neurospheres (originated from SLRP+ t8 CSC-like) showed lower proliferation rates than primary neurospheres. Interestingly, the SLRP+ CSC-like from the @entity463 and @entity521 neurospheres were resistant to @entity2903 ( @entity2904 ) at concentrations >750  M. Our results suggest that @entity463 and @entity521 CSC-like promote the activation of huge quantities of SLRP in response to CSC enrichment, simultaneously acquiring @entity2904 resistance, cellular heterogeneity, and a quiescent phenotype, suggesting a novel pivotal role for SLRP in drug resistance and cell plasticity of CSC-like, allowing cell survival and ECM/niche modulation potential.
