The transcriptome expression differences between GDNF-treated and anti-NCAM1-treated EO771-tdT-LM2 cells under glucose-deprived media treatment

The molecular mechanisms that regulate breast cancer cell (BCC) metastasis and proliferation within the leptomeninges (LM) are poorly understood, limiting development of effective therapies. Here we show that BCCs in mice can invade the LM by abluminal migration along blood vessels that connect vertebral/calvarial bone marrow and meninges, bypassing the blood-brain barrier. This process is dependent on BCC engagement with vascular basement membrane laminin through expression of the neuronal pathfinding molecule integrin α6. Once in the LM, BCCs co-localize with perivascular meningeal macrophages and induce their expression of the pro-survival neurotrophin, GDNF. Intrathecal GDNF blockade, macrophage-specific GDNF ablation, or deletion of the GDNF receptor, NCAM, from BCCs, inhibit BC growth within LM. Here, we performed RNA-seq analysis of GDNF-treated and/or anti-NCAM1-treated EO771-tdT-LM2 cells under glucose-deprived media treatment.