Figure 5
Sensitivity of breast cancer stem cells and bulk tumor volume to therapy is unique between parental HER2+ and transformed resistant cells in vivo.
(A) NOD/SCID mice bearing 40 mm3 BT474 PTEN− LTT xenografts were randomized into treatment groups, 50 mg/kg SF and 10 mg/kg Doc were sufficient to significantly reduce bulk tumor volume within 10 days. Trastuzumab treatment produced no significant reduction in tumor volume for BT474 PTEN− LTT xenografts over the course of the experiment. *p ≤ 0.05. (B) Tumor volume of mice bearing primary BT474 xenografts, 30 doses of SF were required to significantly reduce tumor volume. Arrow denotes the beginning of treatment in primary mice. *p ≤ 0.05. (A,B) Tumor volume represented SD of N = 6 mice. (C) Representative H&E staining of primary BT47 and BT474 PTEN− LTT tumors. SF treatment in BT474 PTEN− LTT xenografts generated intratumoral regions of necrosis (red arrows) whereas this was not observed in BT474 xenografts. Primary xenografts were removed, dissociated and serially reimplanted into secondary mice to determine the tumor initiating CSC frequency by extreme limiting dilution analysis of primary (D) BT474 PTEN− LTT and (E) BT474 xenografts. (F) Tumor formation rate of mice injected with 50,000 BT474 PTEN− LTT cells followed 2 days later by daily SF treatment. Control N = 16, 10 mg/kg N = 16, 50 mg/kg N = 12. (F) Average volume of BT474 PTEN− LTT xenografts that formed with adjuvant treatment. Control N = 16, 10 mg/kg N = 9, 50 mg/kg N = 4.
