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

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.

• Authors: Dario Marchetti, Rebecca Aucoin, Jason Blust, Brian Murry, Andrea Greiter-Wilke
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 91 Issue 1 Pg. 206-15 (Jan 01 2004) ISSN: 0730-2312 [Print] United States
• PMID: 14689592 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2003 Wiley-Liss, Inc.

Chemical References

• Nerve Growth Factors
• Receptor, Nerve Growth Factor
• Receptors, Nerve Growth Factor
• heparanase
• Glucuronidase

Topics

• Animals
• Brain Neoplasms (metabolism, secondary)
• Cell Survival (drug effects, physiology)
• Flow Cytometry
• Glucuronidase (metabolism)
• Humans
• Melanocytes (metabolism)
• Melanoma (metabolism)
• Mice
• Nerve Growth Factors (pharmacology)
• Receptor, Nerve Growth Factor
• Receptors, Nerve Growth Factor (metabolism)
• Signal Transduction (physiology)
• Skin Neoplasms (metabolism)
• Tumor Cells, Cultured