Extended Data Fig. 9: E-cad loss is associated with increased apoptosis at several stages of metastasis in vivo.
From: E-cadherin is required for metastasis in multiple models of breast cancer
a, CC3 immunoreactivity was used to detect the relative abundance of apoptosis in transplanted adeno-Cre-transduced MMTV-PyMT; Cdh1+/+ or Cdh1fl/fl tumours. b, Representative micrographs of E-cad+ primary tumours depicting the rarity of CC3+ cancer cells within the tumour bulk, invasion or dissemination events (magnified insets; scale bar, 20 μm). Scale bar, 50 μm. c, Representative micrographs of E-cad− primary tumours depicting a significant proportion of CC3+ cancer cells within the tumour bulk, dissemination events and invasion (magnified insets; scale bar, 20 μm). Scale bar, 50 μm. d, The number of CC3+ cancer cells within E-cad− primary tumours increases significantly relative to E-cad+ primary tumours. Horizontal line shows the median. ***P = 0.0008 (Mann–Whitney test, two-sided). e, Left, representative micrographs marking CC3+ cancer cells within E-cad+ or E-cad− metastases. Scale bar, 20 μm. Arrowhead, CC3+, E-cad− metastasis. Right, there is a significant increase in the amount of apoptosis in E-cad− metastases relative to E-cad+ metastases. Horizontal line shows the median. *P = 0.015 (Mann–Whitney test, two-sided). f, Schema of colony-formation assay using MMTV-PyMT; E-cad+ or E-cad− cancer cells in the presence of 100 nM or 1 μM of doxorubicin, paclitaxel and cisplatin. g, E-cad− cancer cells are no more or less sensitive to chemotherapies compared to E-cad+ cancer cells. Data are mean ± s.d. **P = 0.0065 (E-cad+), 0.0044 (E-cad−) and ***P = 0.0005 (Ecad+), 0.0003 (E-cad−) (Kruskal–Wallis test).
