Figure 1.

Elimination of senescent host stromal cells reduces palbociclib-enhanced seeding of E0771 TNBC cells in the mouse lung. (A) Experimental schematic: Female C57BL/6 mice received 10 days of 150 mg/kg palbociclib daily by oral gavage (10 doses) or vehicle, followed by a 96 h drug washout period and intravenous injection of 10⁶ E0771 cells in the tail vein. Mice were then monitored for 24 days and euthanized. (B) Representative H&E-stained lung sections and quantification of cross-sectional lung area of histological section occupied by E0771 metastases from the design described in (A). n = 5 mice per group; mean ± standard error indicated. * p < 0.05 by unpaired t-test; scale bars 2 mm. (C) Experimental schematic: Female ATTAC mice received 10 days of 150 mg/kg palbociclib daily by oral gavage (10 total doses), AP20187 (AP) 2 mg/kg every three days by intraperitoneal injection (four total doses), and both palbociclib and AP or vehicle control throughout, followed by a 96 h drug washout period and injection of 10⁶ E0771 cells intravenously in the tail vein. Following injection, mice were monitored for 15 days and then euthanized. (D) Quantification of E0771 metastases as a percentage of cross-sectional lung area on histological section and as a count of metastatic foci per mm² of lung area. Veh = vehicle (n = 3 mice), AP = AP20187 (n = 2 mice), Pal = palbociclib (n = 3 mice), Pal + AP = combination treatment (n = 3 mice); compared by one-way ANOVA with Tukey’s multiple comparisons test: * p < 0.05; ** p < 0.01. (E) Representative H&E-stained lung sections from experiment described in (C); scale bars 2 mm.