When melanoma cells metastasize to the brain, the malignant cells depend on the protein amyloid beta to survive and spread, according to new research from the New York University (NYU) Grossman School of Medicine and NYU Langone Health.
Published in Cancer Discovery, the researchers reported that amyloid beta, known to build up in the brains of Alzheimer's patients, not only helps the cancer survive but also ramps down the immune response that would typically be triggered by the presence of cancer cells.
The study authors focused on melanoma because it metastasizes to the brain in 40% of patients with advanced disease, which is the highest rate among common types of cancers.
In tissue culture and mouse studies, the researchers found that metastatic melanoma cells recovered from human brains and grown in tissue cultures produced approximately three times as much amyloid beta as cancer cells that had metastasized to other parts of the body.
The researchers also showed a beta secretase inhibitor known to reduce amyloid beta levels, LY2886721, decreased the size of brain melanoma metastases by roughly half in mice that were studied.
"Our study reveals an unexpected role for tumour-secreted amyloid beta in promoting the survival of melanoma brain metastases, and suggest a new way to counter it," senior study author Eva Hernando, PhD, professor in the Department of Pathology and assistant dean for Research Integration at NYU Langone Health, said in the press release.
Additional findings revealed that melanoma cells that lacked amyloid beta could not divide and multiply because they were attacked by immune cells at the micro-metastases stage.
The researchers also learned that amyloid beta released by melanoma cells changes gene expression in astrocytes, causing the astrocytes to emit proteins that contribute to a diminished immune response to cancer.