Regulation of p65 nuclear localization and chromatin states by compressive force
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View abstract on PubMed
Summary
This summary is machine-generated.Tumor microenvironment (TME) research shows that mechanical forces and chemical signals, like tumor necrosis factor-alpha (TNFα), interact to affect stromal fibroblasts. This interaction influences tumor progression and offers new therapeutic targets.
Area Of Science
- Oncology
- Cell Biology
- Biophysics
Background
- The tumor microenvironment (TME) is crucial for tumor growth and metastasis.
- Stromal fibroblasts play a key role in TME evolution and tumor progression.
- Current therapies targeting stromal fibroblasts are limited by poor understanding of TME signaling.
Purpose Of The Study
- To investigate the cross-talk between chemical and mechanical signaling in stromal fibroblasts within the TME.
- To develop a novel coculture model mimicking TME conditions for studying stromal cell responses.
Main Methods
- A coculture assay was designed with YFP-TNFα releasing spheroids embedded in collagen gels with fibroblasts.
- The model aimed to replicate the stromal response to tumor signals and mechanical stress.
- Nuclear translocation of p65 and cytoskeletal changes in fibroblasts were analyzed under varying conditions.
Main Results
- Tumor necrosis factor-alpha (TNFα) induced nuclear translocation of p65 in stromal fibroblasts.
- Compressive stress intensified the p65 nuclear translocation.
- Combined mechanical and chemical signaling led to cytoskeletal disruption and altered chromatin state in fibroblasts.
Conclusions
- There is significant cross-talk between cytokine signaling and mechanical forces affecting stromal cells in the TME.
- The developed spheroid model effectively mimics TME conditions for studying stromal cell behavior.
- Understanding this cross-talk is vital for developing effective therapeutic interventions targeting stromal fibroblasts.
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