Cancer: protein processing aids the spread of malignant gliomas

Malignant gliomas are diffuse and highly invasive tumors arising from glial cells in the central nervous system. Persons with malignant gliomas have a poor prognosis, with an average patient survival rate of less than 1 year. The p75 neurotrophin receptor (p75^NTR) is one crucial regulator of glioma invasiveness. Here, Wang et al. investigate the mechanism underlying neurotrophin-mediated tumor invasiveness. Glioma cells expressing either wild-type or cleavage-resistant p75^NTR were implanted into mouse brains and, in contrast to typical glioma infiltration, cleavage-resistant p75^NTR cells formed well-defined tumors. Furthermore, inhibition of the cleavage enzyme γ-secretase prevented tumor cell invasion and prolonged survival in the mice implanted with wild-type p75^NTR cells. In combination with in vitro experiments using patient tumor samples, these studies demonstrate that proteolytic processing of p75^NTR is a major mechanism underlying glioma invasiveness and that targeting γ-secretase might be key in preventing the spread of these tumors.