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3D pentaculture model unveils malignant cell-driven macrophage polarization in high-grade serous ovarian cancer - PubMed

5 hours ago
  • #ovarian cancer
  • #tumor microenvironment
  • #3D cell culture
  • A 3D pentaculture model was developed to replicate the human tumor microenvironment (TME) of high-grade serous ovarian cancer (HGSOC).
  • The model incorporates five human cell types: malignant HGSOC cells, primary fibroblasts, mesothelial cells, adipocytes, and monocytes that differentiate into macrophages without added cytokines.
  • Macrophage clusters in the model mirror those found in patient HGSOC metastases, with proportions varying based on the malignant cell line used.
  • The model enables analysis of how malignant cell heterogeneity (genomic, transcriptomic, proteomic) influences the TME and interactions with macrophages.
  • Targeting 'do-not-eat-me' signals with anti-CD47 and anti-CD24 antibodies showed differential effects on macrophage activity and cancer cell viability, dependent on the malignant cell line.
  • Real-time microscopy confirmed dynamic modulation of macrophage behavior, highlighting the model's utility for studying malignant cell control over TME elements, particularly myeloid interactions.