A novel HLA-G/SPAG9/STAT3 axis promotes brain metastases

Transcriptomic analyses of early-stage brain metastatic cells reveals essential genes that promotes brain metastases, which are targetable. We utilized early passage brain metastasis cell lines derived from primary patient samples of lung-to-brain, breast-brain and melanoma-brain metastases in our work, as these samples are enriched for brain metastasis initiating cells (BMICs) that have already successfully completed the metastatic process. Previous work in our lab successfully established preclinical models of lung-to-brain BM(Nolte, et al., 2013; Singh, et al., 2017). We followed up on this work here by establishing preclinical models of breast-brain and melanoma-brain metastases. Briefly, we injected mice through fatpad and subcutaneous routes, which forms tumors that progresses through the breast-brain and melanoma-brain metastatic stages. Brains from these mice were harvested at orthotopic tumor endpoints that allowed for the identification and capture of pre-metastatic breast (BMFP)and melanoma (BMSC) BMICs respectively. RNA was extracted from these cells and submitted for RNA seq analysis. This work describes the role of a top hit (HLA-G) in brain metastases. HLA-G was identified through transcriptomic analyses of premetastatic lung, breast and melanoma BMICs.