{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T01:00:29Z","timestamp":1793322029657,"version":"4.5.0"},"reference-count":85,"publisher":"American Association for Cancer Research (AACR)","issue":"5","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>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 with those derived from extracranial metastases. We showed that melanoma cells require amyloid beta (A\u03b2) for growth and survival in the brain parenchyma. Melanoma-secreted A\u03b2 activates surrounding astrocytes to a prometastatic, anti-inflammatory phenotype and prevents phagocytosis of melanoma by microglia. Finally, we demonstrate that pharmacologic inhibition of A\u03b2 decreases brain metastatic burden.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>Our results reveal a novel mechanistic connection between brain metastasis and Alzheimer's disease, two previously unrelated pathologies; establish A\u03b2 as a promising therapeutic target for brain metastasis; and demonstrate suppression of neuroinflammation as a critical feature of metastatic adaptation to the brain parenchyma.<\/jats:p>\n                    <jats:p>This article is highlighted in the In This Issue feature, p. 1171<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-21-1006","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T08:05:59Z","timestamp":1646813159000},"page":"1314-1335","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Melanoma-Secreted Amyloid Beta Suppresses Neuroinflammation and Promotes Brain Metastasis"],"prefix":"10.1158","volume":"12","author":[{"given":"Kevin","family":"Kleffman","sequence":"first","affiliation":[{"name":"1Department of Pathology, NYU School of Medicine, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Levinson","sequence":"additional","affiliation":[{"name":"1Department of Pathology, NYU School of Medicine, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0491-1269","authenticated-orcid":false,"given":"Indigo 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