APA
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Kleffman, K., Levinson, G., Rose, ***I. V. L., Blumenberg, L., Shadaloey, S., Dhabaria, A., … Hernando, E. (2022). Melanoma-secreted Amyloid Beta Suppresses Neuroinflammation and Promotes Brain Metastasis. Cancer Discovery.
Chicago/Turabian
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Kleffman, K., G. Levinson, ***IVL. Rose, L. Blumenberg, S. Shadaloey, A. Dhabaria, E. Wong, et al. “Melanoma-Secreted Amyloid Beta Suppresses Neuroinflammation and Promotes Brain Metastasis.” Cancer Discovery (2022).
MLA
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Kleffman, K., et al. “Melanoma-Secreted Amyloid Beta Suppresses Neuroinflammation and Promotes Brain Metastasis.” Cancer Discovery, 2022.
BibTeX Click to copy
@article{k2022a,
title = {Melanoma-secreted Amyloid Beta Suppresses Neuroinflammation and Promotes Brain Metastasis.},
year = {2022},
journal = {Cancer Discovery},
author = {Kleffman, K. and Levinson, G. and Rose, ***IVL. and Blumenberg, L. and Shadaloey, S. and Dhabaria, A. and Wong, E. and Galán-Echevarría, F. and Karz, A. and Argibay, D. and von Itter, R. and Floristan, A. and Baptiste, G. and Eskow, NM. and Tranos, JA. and Chen, J and y Saenz de Miera, EC. Vega and Call, ME. and Rogers, R. and Jour, G. and Wadghiri, Y. and Osman, I. and Li, Y-M. and Mathews, P. and Demattos, R. and Ueberheide, B. and Ruggles, K. and Liddelow, SA. and Schneider, R. and Hernando, E.}
}
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. Our unbiased proteomics analysis of 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 (AB) for growth and survival in the brain parenchyma. Melanoma-secreted AB activates surrounding astrocytes to a pro-metastatic, anti-inflammatory phenotype and prevents phagocytosis of melanoma by microglia. Finally, we demonstrate that pharmacological inhibition of AB decreases brain metastatic burden.
