Ovarian cancer is the most lethal gynaecologic cancer, in large part because of its early dissemination and rapid development of chemotherapy resistance.
Spheroids are clusters of tumor cells found in the peritoneal fluid of patients that are thought to promote this dissemination.
in vitro experiments
Spheroids can be produced from many cancer cell lines under conditions that favor cell-cell over cell-matrix adhesion Not all cancer cell lines form spheroids, and the features that allow spheroid growth are not well characterized.
resistance
A major property is the resistance of spheroid cells to cytotoxic drugs compared to the same cells grown as monolayers
drug resistance is proposed to arise from one or more factors, including creation of a physical barrier to drug penetration; induction of genes or signalling pathways that enhance survival, such as drug efflux pumps; and selection for a subpopulation of drug-resistant cells, which could include cancer stem cells
–>In the experiments in the paper, the resistance could be completely reversed by dissociating the spheroids.
spheroid formation
Current models suggest that spheroids form by aggregation of single tumor cells shed from the primary tumor. Another mechanicsm is clonal expansion.
Here, we demonstrate that spheroids can also form by budding directly as adherent clusters from a monolayer
Their experiment suggests that the ability to form budded spheroids does not require supplemental serum or growth factors added to the spheroid media.
Spheroid budding correlates with epithelial to mesenchymal transition (EMT) markers