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Cerebrospinal fluid microRNA profile in leptomeningeal metastasis patients [LM vs non-LM]

ABSTRACT: This study aimed to identify specific CSF miRNAs for diagnosing and monitoring leptomeningeal metastasis with lung adenocarcinoma. In discovery phase, we performed miRNA microarray analysis in CSF samples from leptomeningeal metastasis patients and non-leptomeningeal metastasis controls.

ORGANISM(S): Homo sapiens

PROVIDER: GSE125191 | GEO | 2020/02/26

REPOSITORIES: GEO

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Cerebrospinal fluid microRNA profile in leptomeningeal metastasis patients [pre- vs post-treatment]

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Phenotypic states of leptomeningeal metastasis

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Phenotypic states of leptomeningeal metastasis

Project description:Leptomeningeal metastasis (LM), or spread of cancer cells into the cerebrospinal fluid, is characterized by a rapid onset of debilitating neurological symptoms and markedly bleak prognosis. The lack of reproducible in vitro and in vivo models has prevented development of novel, LM-specific therapies. Although LM allows for longitudinal sampling of floating cancer cells with a spinal tap, attempts to culture patient-derived leptomeningeal cancer cells have not been successful. We therefore employ leptomeningeal derivatives of human breast and lung cancer cell lines that reproduce both floating and adherent phenotypes of human LM in vivo and in vitro. We introduce a trypsin/EDTA-based fractionation method to reliably separate the two cell subsets and demonstrate that in vitro cultured floating cells have decreased proliferation rate, lower ATP content, and are enriched in distinct metabolic signatures. Long-term fractionation and transcriptomic analysis suggest a high degree plasticity between the two phenotypes in vitro. Floating cells colonize mouse leptomeninges more rapidly and associate with shortened survival. In addition, patients harboring LM diagnosed with CSF disease alone succumbed to the disease earlier than patients with adherent (MRI-positive) disease. Together, these data support mechanistic evidence of a metabolic adaptation that allows cancer cells to thrive in their natural environment but leads to death in vitro.

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