Figure 7.
MET induction is accompanied by robust tumor regression and reduced metastatic burden
(A–C) MMTV-PyMT tumor-bearing female mice were treated with vehicle, paclitaxel (20 mg/kg), vinorelbine (7 mg/kg), or eribulin (1.6 mg/kg) twice weekly to assess (A) tumor growth rate, (B) tumor metastasis to the lungs (red arrows), and (C) EMT status using immunofluorescence of E-cad (green) and vimentin (red). Tumors and lungs were harvested after 2 weeks of drug treatment and a 1-week drug holiday.
(D–F) MMTV-PyMT mice were treated as in (A), and palpable mammary tumors were surgically resected. After a 2-week drug holiday, mice were treated with a second round of therapy to assess tumor growth rate (D), EMT status (E), and tumor metastasis to lungs (F). Tumors and lungs were harvested after a 1-week drug holiday.
(G–N) NSG female mice bearing bilaterally implanted JAX-98naive or NCCC-470NAC orthotopic tumors were treated and assayed as in (A)–(F). After a 2-week treatment regimen (G and K), one tumor was resected from each mouse for molecular analysis (H and M). Mice were then maintained until an orthotopic tumor resumed growth and treated with a second round of therapy to assess tumor growth rate (I and L). Mice were maintained for an additional 3 months prior to tissue harvest to evaluate metastasis (J and N).
(O–Q) MDA-MB-231/Luc-ZsGreen cells were injected into the tail vein. Tumor burden was measured by bioluminescence imaging 2 weeks post injection (baseline) and after 2 weeks of drug treatment. Lung metastatic burden was quantified by counting metastases in H&E-stained sections.
Tumor volumes are shown as mean of 5 mice/group ± SEM. ∗p < 0.05, ∗∗p < 0.001, ∗∗∗p < 0.0005, ∗∗∗∗p < 0.0001 by Tukey-adjusted pairwise comparison.