FIGURE 9:

OCMetSim-Spheroids model predicts that Rac1 contributes to ovarian cancer spheroid intravasation into circulation and extravasation to distant niche sites. Experiment 1a: Spheroid simulation results comparing (A) the number of spheroids and (B) the rate at which they enter the distant niche site for Rac1 OE or KD clone 23. Rac1 OE or KD spheroids were given 100% probability of adhesion, based on 100% spheroid adhesion observed in the mesothelial clearance assay. (A) Varying probabilities of cells death in the blood decreased the number of ovarian cancer spheroids in the metastatic niche. (B) The rate at which the OE and KD spheroids reached the metastatic niche decreased with increasing probability of cell death in the blood; however, the Rac1 OE spheroids reached the distant site faster than the KD spheroids. Experiment 2a: Spheroid simulation results comparing cell crowding and cell death from crowding (C, D). (C) With added cell death from crowding, the number of Rac1 OE and KD cells that reached the distant site decreased. (D) With crowding and cell death due to crowding, the rate at which the Rac1 OE spheroids reached the distant site was decreased compared with no crowding. The rate at which the Rac1 CRISPR-Cas9 KD cells reached the distant site was decreased with added cell death from crowding. Thirty simulations were run for each experiment. Error bars represent means ± SD. Two-way ANOVA followed by Tukey’s post-hoc test for multiple comparison across columns and rows was used to compare cell types and crowding and crowding death: *p < 0.05, ***p < 0.005 ****p < 0.0001.