University of Twente Student Theses
Cancer associated fibroblasts mediate formation of heterotypic circulating tumour cell clusters
Noll, M.R. (2025) Cancer associated fibroblasts mediate formation of heterotypic circulating tumour cell clusters.
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| Abstract: | Circulating tumour cells (CTCs) are instrumental for the metastatic spread of cancer, which accounts for the vast majority of cancer deaths. The metastatic success of CTCs hinges foremost on their capacity to survive the environmental conditions within the bloodstream, which is generally poor for primary tumour cells. This study includes a literature review concerning the various survival mechanisms presented by CTCs that enhance their metastatic capacity, including epithelial-to-mesenchymal transition (EMT), recruitment of platelets or other cell types and incorporation of cells into cellular aggregates, referred to as CTC clusters. Experimental studies are included, inspired by the literature review, concerning the formation and characterization of homotypic and heterotypic CTC clusters produced artificially by (co-)culturing the MCF-7 and MDA-MB-231 breast cancer and the HMF mammary fibroblast cell lines in agarose microwell arrays. The size of the CTC cluster was similar among the combinations of incorporated cell lines and could be controlled by adjusting the initial seeding density. Strikingly, MDAMB- 231 cells could not be incorporated into homotypic clusters or heterotypic clusters in combination with MCF-7 cells, but were incorporated into heterotypic clusters with HMF cells. Moreover, the respective distribution of MCF-7 and MDA-MB-231 cells in heterotypic HMF/breast cancer clusters indicates that MDA-MB-231 and HMF cells express intercellular adhesion proteins that interact more favourably with each other than themselves, whereas the opposite was observed for the combination of MCF-7 and HMF cells. Together, this study presents the production of homotypic and heterotypic breast cancer tumour cell clusters from cell lines as an easily producible bottom-up model for CTC clusters. Moreover, these findings indicate that fibroblasts uniquely facilitate CTC cluster formation by enhancing intercellular adhesion. |
| Item Type: | Essay (Master) |
| Faculty: | TNW: Science and Technology |
| Subject: | 42 biology |
| Programme: | Biomedical Engineering MSc (66226) |
| Link to this item: | https://purl.utwente.nl/essays/106376 |
| Export this item as: | BibTeX EndNote HTML Citation Reference Manager |
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