Fig. 5

AF38469 inhibits progranulin domain A-induced breast cancer metastases and local infiltrative growth in vivo. MDA-MB 231-luc xenografts were injected with either vehicle (PBS) or 8 μg of GRN A three times per week for 6 weeks by subcutaneous injection. Mice were separated into groups (vehicle (n = 5), GRN A (n = 5), vehicle + AF38469 (n = 4) and GRN A + AF38469 (n = 5)). The sortilin inhibitor AF38469 or vehicle control was administered in drinking water at concentrations of 5 μg/mouse/day (n = 2) and 10 μg/mouse/day (n = 3). 5–10 μg AF38469 groups were pooled (total n = 5). a Tumour burden and (b) lung metastases luciferase measurements at the experimental endpoint are expressed as mean photons/second (top and bottom, respectively). Mann-Whitney U test where used for statistics. *p < 0.05. c (Bottom) Macroscopic visualisation of ulcerating tumours in AF38469-treated or vehicle-treated mice. (Top) Fraction of mice with tumour ulceration of mice injected with 8 μg of GRN A or GRN A in combination with AF38469 (n = 9). d Immunohistochemical analyses of the GRN A- and AF38469-treated groups of MDA-MB 231 luc xenografts with skin was performed using Ki67 and haematoxylin staining. Scale bar represents 5 × 250 μm. GRN granulin