ROME expression drives metastasis development in vivo. A, Timeline of tail vein metastasis experiments. B, In a tail vein metastasis model, mice injected with ROME-overexpressing TC-71 cells (n = 11) had a higher total mass of metastatic nodules than did controls (n = 10). C, In a tail vein metastasis model, mice injected with ROME-KO TC-71 cells (n = 11) had a lower total mass of metastases than controls injected with WT TC71 cells (n = 11). Statistical significance was determined via an unpaired t test (one-tailed) for B and C. D, Diagram of the orthotopic Ewing sarcoma leg amputation experimental timeline. E, Representative gross images of lungs from mice injected with TC-71 cells overexpressing ROME or with EV (left) with quantification (middle). Representative images of H&E staining are shown on the right confirming metastatic nodules in the lungs of SCID mice. Statistical significance was calculated by the Fisher exact test (one-sided). F, TC-71 ROME-KO cells displayed significantly reduced primary tumor recurrence [n = 10 per group, log-rank (Mantel–Cox) test]. G, ROME is expressed throughout many different tumor types (CNS, central nervous system; HEPAC, hepatocellular carcinoma and cholangioma; KICH, kidney chromophobe and other renal carcinoma; KIPCC, papillary cell renal carcinoma; OV, ovarian cystadenocarcinoma; PAAD, pancreatic ductal adenocarcinoma; PCPG, pheochromocytoma and paraganglioma; SCC/BLCA, squamous cell or bladder carcinoma; TGCT SEM, testicular germ cell tumor, seminoma). H, Kaplan–Meier curves of patient survival stratified by high (red line) and low (black line) ROME expression (from the Kaplan–Meier plotter database). [A and D, Created in BioRender. Lab, S. (2026) https://BioRender.com/atgnfw0.]
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