BSLD-03 MIMICKING CAFS, PIAL CELLS SUPPORTLEPTOMENINGEAL METASTASIS

Abstract Leptomeningeal metastasis (LM), the spread of cancer into cerebrospinal fluid (CSF)-filled coverings brain and spinal cord, is a dismal complication leading to rapid neurologic disability death. While diverse array primary tumors may result in LM, recent work from our laboratory (Chi Y et al 2020 Science) demonstrates conserved transcriptional signature, independent tumor, suggesting that tumor-microenvironmental interactions play dominant role this pathology. We have proteomically interrogated CSF collected breast (n = 45), lung 30), melanoma 27) patients with without LM. detect robust expression inflammatory cytokines all LM+ samples, 15 these including IL8, IL6, CXCL1 are across tumor types presence Because cells do not express mRNA associated cytokines, we hypothesized originate microenvironment. Within leptomeninges, LM adhere interact innermost layer meninges, pia mater, which contains fibroblast-like cells. Co-culture pial induced changes cell transcriptome secretome, increased production. This communication between preserved absence direct cell-cell contact. These support growth vivo, as measured by co-implantation experiments. In addition, bulk RNA sequencing mouse shows an signature upregulated Taken together, observations cancer-associated-fibroblast like for setting Our extends CAF phenotype beyond classical fibroblasts include cells, novel therapeutic opportunities within CNS malignancies.