Fig. 5.

Systemic inhibition of either IL1β or Wnt signalling prevents bone metastasis in vivo. a Anti-mouse IL1β treatment reduced hind limb bone metastases in a spontaneous MDA-MB-231_BH mouse model. Histology shows tumour cells in bones of control mice (M1, M2) vs. tumour free hind limbs in treated mice (M9, M16). Tumour areas are marked as T. Scale bar 500 µM. Statistical significance assessed by chi squared test, tumour vs. no tumour in treated vs. untreated mice. b Anti-IL1β treatment increased trabecular bone volume at experiment termination. Example images presented from a control mouse (M3) and a mouse treated with IL1β antibody (M11). Data presented as percentage bone volume/total volume (%BV/TV) (n = 8). c Vantictumab treatment reduced spontaneous hind limb bone metastases in the MDA-MB-231_BH model. Histology shows tumour cells in bones of control mice (M15, M19) vs. tumour free hind limbs in treated mice (M1, M2). Tumour areas are marked as T. Scale bar 500 µM. Statistical significance assessed by chi squared test, tumour vs. no tumour in treated vs. untreated mice. d Vantictumab treated mice showed a thinning of cortical and spongy bone. Representative images of control mice (M11, M15) and Vantictumab treated mice (M5, M7) are presented. Arrows denote areas of bone loss. e No significant difference in the number of DiD labelled tumour cells in control and Vantictumab treated mice was seen 30 days following injection of tumour cells (n = 4 control, n = 5 Vantictumab treated). f Anakinra reduced hind limb tumours in an ER + PDX (BB3RC32) model following intra-cardiac injection of tumour cells. Histology shows tumour cells in bones of control mice (M23, M28) vs. tumour free hind limbs in treated mice (M12, M15). Tumour areas are marked as T. Scale bar 500 µM. Statistical significance was assessed by chi squared test, tumour vs. no tumour in treated vs. untreated mice. g Our proposed model of signalling pathways underpinning bone colonisation by metastatic breast cancer cells. All graphs represent mean ± SEM, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001