1. Supplementary Figure 1 a b RANK 1 2 3 4 5 6 7 8 9 10 11 * RANK Arbitrary Score ns 0 1 2 3 Normal breast Primary tumor Metastasis lymph node *

2. ac d Supplementary Figure 2 Day 3Day 1 3 H thymidine uptake (CPM) 0 40000 60000 80000 100000 120000 20000 RANKL RANKL / OPG Control Anisomycin Control UV Sorbitol % survival 0 10 20 30 40 50 60 RANKL Control RANKL Prolactin pERK1/2 pAKT AKT pSTAT5 STAT5 0 5 10 20 40 min 5 10 20 40 pERK1/2 -Actin ERK1/2 RANKL 0 5 10 30 60 min RANK b e

3. Supplementary Figure 3 % increased migration RANKL [1 g/ml] RANKL [2.5 g/ml] SDF-1 [0.1 g/ml] RANKL [2.5 g/ml] SDF-1 [1 g/ml] RANKL [2.5 g/m] 0 20 40 60 80 100 120

4. a bc Migration toward the tip, mm -40 0 40 80 120 160 Control RANKL OPG * Supplementary Figure 4 ControlRANKL ControlRANKL

5. RANK -actin 12 c RANKL RANKL / OPG RANKL / -CXCR4 SDF-1 -CXCR4 SDF-1 OPG SDF-1 10 20 30 40 50 60 70 0 % increased migration * * Supplementary Figure 5 a ERK1/2 RANKL SDF-1 0 3 10 30 60 120 min 0 3 10 30 min pERK1/2 d b 0 10 20 30 40 50 60 70 80 90 100 % migration % increased migration 20 40 60 80 100 0 SDF-1 RANKL 6Ckine 6Ckine / RANKL CTACK CTACK / RANKL SDF-1 / RANKL * *

6. Supplementary Figure 6 a c TibiaVertebra TumorControl b * 0 100 200 300 400 500 600 700 Total Trabecular Cortical Bone density (pQCT mg/cm 3 ) Control B16F10

7. Supplementary Figure 7 ControlTumorTumor / OPG * * abc def ghi * *