Multicellular ovarian cancer spheroids: novel 3D model to mimic tumour complexity

• Published in: Scientific reports Vol. 14; no. 1; pp. 23526 - 18
• Main Authors: Flörkemeier, Inken, Antons, Lisa K., Weimer, Jörg P., Hedemann, Nina, Rogmans, Christoph, Krüger, Sandra, Scherließ, Regina, Dempfle, Astrid, Arnold, Norbert, Maass, Nicolai, Bauerschlag, Dirk O.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09-10-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67/327; 631/67/70; Antineoplastic Agents - pharmacology; Cancer-Associated Fibroblasts - metabolism; Cancer-Associated Fibroblasts - pathology; Cell culture; Cell Line, Tumor; Cell Proliferation; Cell size; Cell Survival; Cisplatin; Cisplatin - pharmacology; Co-culture model; Coculture Techniques - methods; Female; Fibroblasts; Fibroblasts - pathology; Humanities and Social Sciences; Humans; Models, Biological; multidisciplinary; Ovarian cancer; Ovarian cancer and fibroblast; Ovarian Neoplasms - pathology; Science; Science (multidisciplinary); Spheroids; Spheroids, Cellular - pathology; Tumor cell lines; Tumor Microenvironment; Tumors; Tumour microenvironment; Co-culture model; Ovarian cancer and fibroblast; Spheroids; Tumour microenvironment
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-73680-6

In vitro
, spheroid models have become well established in cancer research because they can better mimic certain characteristics of
in vivo
tumours. However, interaction with the tumour microenvironment, such as cancer-associated fibroblasts, plays a key role in tumour progression. We initially focused on the interaction of tumour cells with fibroblasts. To model this interaction, we developed a spheroid model of ovarian cancer and fibroblasts. To this end, ovarian cancer cell lines and
ex vivo
primary cells were simultaneously and sequentially seeded with fibroblasts in a scaffold-free system at different ratios and subsequently characterized with respect to changes in morphology, proliferation, and viability. We demonstrated that co-cultures are able to form by far more compact spheroids, especially in cells that form aggregates in mono-culture. In addition, the co-cultures were able to increase proliferation and sensitivity to cisplatin. Simultaneous seeding led fibroblasts invade the core in both cell lines and primary cells. These results show differences in formation, firmness, and size between co-culture and mono-culture. Our model is designed to better represent and characterize the mutual influencing factors of fibroblasts and tumour cells. Fibroblast-supplemented multicellular spheroids are a valuable tool for tumour microenvironment interaction and new drug discovery.