Role of Perilesional Reactive Astrocytosis in Melanoma Brain Metastases
Abstract
Melanoma is the deadliest form of skin cancer, and U.S. Military personnel are at an increased risk due to occupational exposures. Melanoma spreads to the brain with a high frequency, where it triggers neurologic symptoms including seizures. While melanoma restricted to the skin is often treatable, if the disease spreads to other organs - especially the brain - prognosis is poor. Once in the brain, melanoma interacts with resident cells including neurons, microglia, and astrocytes. We are particularly interested in interactions with the astrocytes, which normally provide pro-survival factors and regulate nutrient and local blood flow. These cells also regulate neuronal excitability by removing neurotransmitters preventing excessive activation and seizures. Following injury or infection, astrocytes also play an immune-like role that is characterized by changes in cell shape, protein expression and the functional support to neurons (called reactive astrocytosis). Reactive astrocytes have been found to surround melanoma brain metastasis at autopsy; however, little is known regarding how these cells influence the growth of melanoma in the brain and their resistance to treatment. Our goal of the current proposal is to understand reactive changes in astrocytes in response to melanoma, how these responses might in turn influence melanoma growth in the brain, and whether treatments targeting reactive astrocytes could be harnessed for better outcomes. This project is a collaborative effort, bringing tools and expertise from the fields of neuroscience and basic cancer biology fields together to highlight the importance of interactions of melanoma brain metastases with cells that form the local brain microenvironment. This work has no potential risks for patients and will directly benefit the men and women of the U.S. military, who have a higher incidence rate for melanoma. The current proposal addresses the Understanding the Tumor Microenvironment Focus Areas of the fiscal year 2022 Melanoma Research Program Idea Award.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310633
Entities
People
- Joshua Jackson
Organizations
- Drexel University
- United States Army