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Biology subjects

Levinson, G.

Publications and source records attributed to Levinson, G..

2 recordsLinked to original sources

MetFinder: a neural network-based tool for automated quantitation of metastatic burden in histological sections from animal models

Diagnosis of most diseases relies on expert histopathological evaluation of tissue sections by an experienced pathologist. By using standardized staining techniques and an expanding repertoire of markers, a trained eye is able to recognize disease-specific patterns with high accuracy and determine a diagnosis. As efforts to study mechanisms of metastasis and novel therapeutic approaches multiply, researchers need accurate, high-throughput methods to evaluate effects on tumor burden resulting from specific interventions. However, current methods of quantifying tumor burden are low in either resolution or throughput. Artificial neural networks, which can perform in-depth image analyses of tissue sections, provide an opportunity for automated recognition of consistent histopathological patterns. In order to increase the outflow of data collection from preclinical studies, we trained a deep neural network for quantitative analysis of melanoma tumor content on histopathological sections of murine models. This AI-based algorithm, made freely available to academic labs through a web-interface called MetFinder, promises to become an asset for researchers and pathologists interested in accurate, quantitative assessment of metastasis burden.

cancer biology↗

Melanoma-secreted Amyloid Beta Supresses Neuroinflammation and Promotes Brain Metastasis

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 performed unbiased proteomics analysis of melanoma short-term cultures, a novel model for the study of brain metastasis. Intriguingly, we found that proteins implicated in neurodegenerative pathologies are differentially expressed in melanoma cells explanted from brain metastases compared to those derived from extracranial metastases. This raised the exciting hypothesis that molecular pathways implicated in neurodegenerative disorders are critical for metastatic adaptation to the brain. Here, we show that melanoma cells require amyloid beta (A{beta}), a polypeptide heavily implicated in Alzheimers disease, for growth and survival in the brain parenchyma. Melanoma cells produce and secrete A{beta}, which activates surrounding astrocytes to a pro-metastatic, anti-inflammatory phenotype. Furthermore, we show that pharmacological inhibition of A{beta} decreases brain metastatic burden. Our results reveal a mechanistic connection between brain metastasis and Alzheimers disease - two previously unrelated pathologies, establish A{beta} as a promising therapeutic target for brain metastasis, and demonstrate suppression of neuroinflammation as a critical feature of metastatic adaptation to the brain parenchyma.

cancer biology↗