Figure 4. Progesterone signalling regulates tumour formation and dissemination in vivo.
(a) Tumour formation 8 weeks after transplantation of PT- or EL-derived spheres into mammary fat pads of wt-BALB/c siblings. (b) Percentage of mice with DCCs (detected by cytokeratin staining) in bone marrow (BM) 8 weeks after transplantation. (c) Number of DCCs in BM of mice 8 weeks after transplantation. (d) DCC counts in BM in recipients transplanted at different age. (e) Time to tumour formation after transplantation of mammary glands (week 4; gland model) or tumour pieces (week 20–22; tumour model). The red box highlights mice from both models with similar tumour growth kinetics, which are analysed separately in Extended Data Fig 6o–q. (f) Percentage of mice with lung macro-metastasis in gland vs. PT model. (g) Macro-metastasis formation in recipient mice with similar tumour growth kinetics (mice enclosed in red box of panel e; see Extended data Fig 6o). (h) Example of a phylogenetic tree (mouse 3769): N, normal cells; P, primary tumour; M1-3, metastases 1–3; A1-3, inferred common ancestors. The ordinate indicates the number of aberrations per profile on a square root scale. (i) Aberration profiles along tree paths from N via A1-3 to P or M1-3 in terms of aberration prototypes (see Extended data Fig 7–9 for details). (j) Distribution of relative “time points” of dissemination on a genetic scale for all 44 primary tumour-metastases pairs. The red line indicates dissemination after which 50% of primary tumour changes were acquired as an arbitrary threshold for early vs late dissemination; see Extended Data Fig 7c). P-values in panel a, c, and d: Student’s t-test; in b,: Fisher’s exact test; in f and g: chi square test; in e: Mann-Whitney test. *, p≤0.05; ***, p≤0.001; ****, p≤0.0001; NS, Not Significant. Panels a, c, d, and e represent medians.