ArticleJournal of translational medicine2025
Insights into spheroid formation: interaction of ovarian cancer cells with macrophage populations in the tumor microenvironment.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Immune Evasion in Ovarian Cancer Peritoneal Metastasis: Mechanisms and Biomarker-Guided Therapeutic Matching.Journal of cellular physiology · 2026Review
- Mechanoresponsive reprogramming of tumor-associated macrophages during cancer progression.Frontiers in cell and developmental biology · 2026Review
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Authors and funding
7 authors.
Funding
Abstract
backgroundTreating advanced ovarian cancer (OC) is challenging due to the immunosuppressive tumor microenvironment. This study investigates tumor-immune cell interactions using organotypic spheroid models that simulate the in vivo microenvironment.
methodsA dual-model spheroid system was established combining serous adenocarcinoma SKOV-3 cells with monocytes, pro-inflammatory (MΦ1) or anti-inflammatory (MΦ2) macrophages, or their derived exosomes (EXOs). In Model A, immune cells or EXOs were co-seeded with tumor cells to replicate early heterotypic aggregation. In Model B, immune cells or EXOs were introduced 24 h post-spheroid formation to simulate immune infiltration into established spheroids. Spheroid morphology was quantified by diameter and circularity, while the distribution of immune cells and EXOs was assessed via fluorescence intensity profiling in 2D and 3D. epithelial-to-mesenchymal transition (EMT) marker expression was analyzed to assess tumor cell phenotypic changes.
resultsSpheroids formed with SKOV-3 cells and ThP-1 monocytes developed a dense monocyte-enriched outer layer. Macrophage subtypes differentially influenced spheroid morphology: MΦ2 macrophages promoted the formation of multiple, loosely organized spheroids and increased N-cadherin expression, indicative of enhanced EMT. Similarly, MΦ-EXOs modulated EMT marker expression, underscoring the contribution of both direct cell interactions and paracrine signaling in regulating spheroid dynamics.
conclusionsMacrophages and their exosomes play a critical role in modulating the architecture and functional behavior of spheroids, reflecting two key aspects of OC progression: the formation of immune cell-enriched spheroids in ascitic fluid and tumor-immune interactions at peritoneal metastatic sites. This model provides a clinically relevant platform for preclinical testing of therapeutic strategies targeting peritoneal dissemination in OC.
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