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Amyloid Beta Promotes Brain Metastasis

ABSTRACT: Brain metastasis is a significant cause of morbidity and mortality in multiple cancer types and represents an unmet clinical need. The mechanisms that mediate metastatic cancer growth in the brain parenchyma are largely unknown. Melanoma, which has the highest rate of brain metastasis among common cancer types, is an ideal model to study how cancer cells adapt to the brain parenchyma. We utilized pairs of brain metastasis-derived (BM) and non-brain metastasis-derived (NBM) melanoma short term cultures (STCs) obtained from the same patient. We performed TMT based multiplexed analysis of these cell lines using off-line fractionation to increase our proteomics coverage. Our unbiased proteomics analysis of these melanoma short-term cultures revealed that proteins implicated in neurodegenerative pathologies are differentially expressed in melanoma cells explanted from brain metastases compared to those derived from extracranial metastases. We showed that melanoma cells require amyloid beta for growth and survival in the brain parenchyma. Melanoma-secreted A beta activates surrounding astrocytes to a pro-metastatic, anti-inflammatory phenotype and prevents phagocytosis of melanoma by microglia. Finally, we demonstrate that pharmacological inhibition of Abeta decreases brain metastatic burden.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Beatrix Ueberheide

PROVIDER: MSV000088814 | MassIVE | Thu Feb 10 08:37:00 GMT 2022

REPOSITORIES: MassIVE

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Amyloid Beta Promotes Brain Metastasis

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