Figure 2. Long-Term Treatment Withdrawal Can Reduce Tumor Growth-Promoting Phenotypes.
(A) Schematic showing combined analysis of ortho-surgical models for differences in (presurgical) PT and (postsurgical) Met growth for ST-W and LT-W conditions normalized to parental cells (top left). Comparisons of SuR/ST-W (red dots), AxR/ST-W (blue dots), and SuR/LT-W or AxR/LT-W (gray dots) cells from LM2–4SuR (SCID; n = 3–6), MeWoSuR (SCID; n = 4), and 4T1AxR (BALB/c; n = 5) shown (all panels). Crossed lines represent the SD of LT-W (gray cross) and ST-W (red or blue cross)-treated data derived from comparisons of PT weight data (vertical dotted line) and OS data (horizontal dotted line). p values for PT burden (Student’s t test) and survival (Kaplan-Meier log-rank) are listed for comparisons between ST-W and LT-W cell lines, with significant values in bold.
(B) Immunofluorescence staining (top) and quantification (bottom) of human vimentin+ LM2–4 cell variants in mouse lung tissue 24 hr after i.v. implantation of P, SuR/ST-W, and SuR/LT-W variants (SCID; n = 8–9).
(C) Survival analysis of SCID mice implanted with ST-W or LT-W variants of LM2–4SuR (SCID; n = 9–10) cells.
SuR, sunitinib-resistant; AxR, axitinib-resistant; PT, primary tumor; Met, metastasis; OS, overall survival; ST-W, short-term withdrawal; LT-W, long-term withdrawal; i.v., intravenous. Su (60 mg/kg/day); Ax (100 mg/kg/day). PT burden was assessed by excised tumor or kidney weight. OS was based on Kaplan-Meier. Quantitative data shown as mean ± SD. *p < 0.05 and ****p < 0.0001.
See also Figure S2.