IL13Rα2 Promotes Proliferation and Outgrowth of Breast Cancer Brain Metastases

PURPOSE: , and postulate IL13Rα2 as a suitable therapeutic target for BM. EXPERIMENTAL DESIGN: . We performed RNAseq and functional studies to define the molecular mechanisms underlying IL13Rα2 function in BCBM. RESULTS: , (ii) marked micrometastasis and invasive fronts in BCBM, and (iii) predicted shorter disease-free survival and BM-free survival (BMFS) in breast primary tumors known to metastasize to the brain. In experimental metastases models, which bypass early tumor invasion, downregulation of IL13Rα2 before or after tumor seeding and brain intravasation decreased BMs, suggesting that IL13Rα2 and the promotion of a proliferative phenotype is critical to BM progression. CONCLUSIONS: Non-genomic phenotypic adaptations at metastatic sites are critical to BM progression and patients' prognosis. This study opens the road to use IL13Rα2 targeting as a therapeutic strategy for BM.