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

✍ Scribed by Dario Marchetti; Rebecca Aucoin; Jason Blust; Brian Murry; Andrea Greiter-Wilke

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 265 KB
• Volume: 91
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.10649

✦ Synopsis

Abstract

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. We report that p75^NTR^ promoted the survival of brain‐metastatic melanoma cells but not melanocytes in stress cultures conditions. Secondly, melanoma cells fluorescently sorted for high p75^NTR^ expression (p75^NTR‐H^ cells) had an up to a 15‐fold greater survival than those sorted for low p75^NTR^ expression (p75^NTR‐L^ cells). Thirdly, cells overexpressing p75^NTR^ associated with the growth fraction and provided these cells with an inherent growth advantage. Finally, we observed an increased survival of sorted p75^NTR‐L^ cells, dependent upon treatment of NT members whose functional receptors are present on these cells. Together, these results delineate that p75^NTR^‐mediated trophic support profoundly affects competitive melanoma‐cell survival when the tumor cell microenvironment becomes growth limiting. © 2003 Wiley‐Liss, Inc.