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Insights into spheroid formation: interaction of ovarian cancer cells with macrophage populations in the tumor microenvironment
,
Jing Xiao,
Deya Gonzalez ,
Steve Conlan ,
Bruna Corradetti
Journal of Translational Medicine, Volume: 23, Issue: 1, Start page: 1192
Swansea University Authors:
Paul Rees , Deya Gonzalez , Steve Conlan
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DOI (Published version): 10.1186/s12967-025-07162-2
Abstract
Background: Treating 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. Methods: A dual-model spheroid system was establi...
| Published in: | Journal of Translational Medicine |
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| ISSN: | 1479-5876 |
| Published: |
Springer Nature
2025
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa70807 |
| Abstract: |
Background: Treating 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. Methods: A 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. Results: Spheroids 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. Conclusions: Macrophages 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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| Keywords: |
Ovarian cancer, Immune cells, Macrophages, Exosomes, Spheroids, Metastatic processes, Image analysis |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
Support for the study was provided by the Golfers Against Cancer Foundation to BC. |
| Issue: |
1 |
| Start Page: |
1192 |