Brain metastases in melanoma: roles of neurotrophins.

Brain metastasis, which occurs in 20% to 40% of all cancer patients, is an important cause of neoplastic morbidity and mortality. Successful invasion into the brain by tumor cells must include attachment to microvessel endothelial cells, penetration through the blood-brain barrier, and, of relevance, a response to brain survival and growth factors. Neurotrophins (NTs) are important in brain-invasive steps.

p75 neurotrophin receptor functions as a survival receptor in brain-metastatic melanoma cells.

The p75 neurotrophin receptor (p75(NTR)), a common receptor for members of the neurotrophins (NT) family, was previously identified as a molecular determinant of brain metastasis. We have also reported that NT treatment of murine and human brain-metastatic melanoma cells affects their invasive capacities and increases the production of heparanase, an important and unique extracellular matrix (ECM) degradative enzyme. Neurotrophism can be a survival-support mechanism for brain-metastatic cells and a survival assay was devised to mimic the growth limiting conditions of rapidly expanding metastatic tumors prior to neoangiogenesis.

Brain-metastatic melanoma: a neurotrophic perspective.

The brain is a unique microenvironment enclosed by the skull and maintaining a highly regulated vascular transport barrier. To metastasize to the brain, malignant tumor cells must attach to microvessel endothelial cells, invade the blood-brain barrier (BBB), and respond to brain survival and growth factors. Neurotrophins (NT) are important in brain invasion because they stimulate this process.