Fig. 10

Model of the effects of sc polarity on metastatic seeding. a Scheme of the compartmental model generated from data shown in Fig. 9d, e, k and Supplementary Fig. 18a. Transfer rates for polarised (pol) and depolarised (dep) cells defined as attachment rate (k_att), adhesion rate (k_adh) and tissue residence rate (k_tiss.res) are shown in Supplementary Figure 19b. b In silico simulation of the decrease of polarised and depolarised cells in the circulation compartment showing that polarised cells leave circulation faster than depolarised cells due to increased attachment and adhesion rates. The number of circulating cells rapidly decreases to 0 as the model does not account for recirculation due to circulatory pressure. c Simulation of attachment of polarised and depolarised cells to substrate. The higher attachment rate of polarised cells leads to a higher peak population as compared to depolarised cells. The rapid decrease in the number of attached cells is a result of the cells adhering and thus leaving the attachment compartment and entering the adhesion compartment. d Simulation of adhesion of polarised and depolarised cells to substrate, showing faster adhesion of polarised cells as compared to depolarised cells. The decrease in the number of adhered cells is a result of the cells extravasating and thus leaving the adhesion compartment and entering the tissue residence compartment. e Simulation of tissue residence of polarised and depolarised cells, showing decreased tissue residence and thus metastatic seeding of depolarised cells mainly due to delayed attachment and adhesion. f Model for possible roles of sc polarity during metastasis. Upon dedifferentiation, detachment and rounding, single cells in the primary tumour form an ezrin-rich pole (i). This pre-polarisation may favour intravasation (ii). During the liquid phase (iii) in blood, lymph or ascites fluid, tumour cells maintain their pole, which can facilitate their attachment by unspecific interaction (iv). Pre-polarisation advances reorientation (v) and transition of the pole into a distal cap (vi). During transmigration (vii) and interstitial migration (viii), the pole establishes the cell rear in all migratory phenotypes