
Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 14, 2024
Language: Английский
Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 14, 2024
Language: Английский
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: July 29, 2024
Abstract The tumor microenvironment (TME), which is composed of various cell types and the extracellular matrix (ECM), plays crucial roles in cancer progression treatment outcomes. However, impact mechanical properties ECM, specifically collagen fibril alignment crosslinking, on macrophage behavior polarization less understood. To investigate this, we reconstituted 3D matrices to mimic physical characteristics TME. Our results demonstrated that stiffening through or crosslinking fibrils promotes toward anti-inflammatory M2 phenotype. This phenotype characterized by increased expression CD105 CD206 a distinct cytokine secretion profile. stiffness aligned activate mechanotransduction pathways, notably integrin β1 PI3K signaling, leading IL-4 secretion, acts an autocrine manner further promote polarization. Interestingly, these stiffened microenvironments also suppressed proinflammatory response. In coculture experiments with breast lines (MDA-MB-231 MCF-7), macrophages within significantly proliferation invasion. These findings suggest its create more favorable environment for modulating activity. Overall, our study underscores critical role ECM mechanics shaping immune TME, highlighting potential therapies target inhibit enhance efficacy.
Language: Английский
Citations
0Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 14, 2024
Language: Английский
Citations
0