TGFβ inhibition during radiation suppresses the Ewing sarcoma metastatic phenotype. A, Tumors were established utilizing the TC32 cell line hu-CD34+ mice. 3 weeks following tumor injection, mice were treated with ± radiotherapy (5 Gy dose × 1) and ± TGFβ inhibition with daily RER injection (or PBS control). CT imaging was obtained starting 1 week following tumor cell injection and then once weekly thereafter. Tumors were allowed to develop until mice met criteria for euthanasia. Tumor volumes were determined utilizing CT imaging (see methods). Growth rate represents the average percent increase in tumor volume per day. Each colored line represents an individual mouse and the black line represents the average growth rate. Day –10 indicates 10 days prior to the start of treatment interventions. Tumor growth curves were estimated by a linear mixed model with a fixed effect for treatment and random effect for mouse. (n = 7 control group, n = 8 radiotherapy only group, n = 9 RER only group, and n = 9 radiotherapy + RER group). B, Schematic of the experimental design for serial sectioning of bilateral lung tissue for the analysis of metastatic disease burden. C, Bilateral lungs were harvested from mice in the experiment from Fig. 5 (n = 9 mice per group) and mice from A (n = 8 control group, n = 8 radiotherapy only group, n = 9 RER only group, n = 7 radiotherapy + RER group). Lung tissue was formalin fixed and paraffin embedded and underwent serial sectioning prior to review by an independent pathologist (see “Materials and Methods”). The number of metastatic foci per serial section was determined. Each bar represents the average number of metastatic lesions across serial section in individual mouse, and error bars represent SD. ***, P P P value ≥ 0.05. RT, radiotherapy. B, Created in BioRender. Daley, J. (2025) https://BioRender.com/cnw56f3.
Daley et al. (Wed,) studied this question.