The
cell-surface receptor protein tyrosine phosphatase mu (
PTPmu) is a homophilic
cell adhesion molecule expressed in CNS neurons and glia.
Glioblastomas (GBMs) are the highest grade of
primary brain tumors with astrocytic similarity and are characterized by marked dispersal of
tumor cells.
PTPmu expression was examined in human GBM, low-grade
astrocytoma, and normal brain tissue. These studies revealed a striking loss of
PTPmu protein expression in highly dispersive GBMs compared to less dispersive low-grade
astrocytomas and normal brain. We hypothesized that
PTPmu contributes to contact inhibition of glial cell migration by transducing signals in response to cell adhesion. Therefore, loss of
PTPmu may contribute to the extensive dispersal of GBMs. The migration of
brain tumor cells was assessed in vitro using a scratch
wound assay. Parental U-87 MG cells express
PTPmu and exhibited limited migration. However,
short-hairpin RNA (
shRNA)-mediated knockdown of
PTPmu induced a morphological change and increased migration. Next, a brain slice assay replicating the three-dimensional environment of the brain was used. To assess migration, labeled U-87 MG
glioma cells were injected into adult rat brain slices, and their movement was followed over time. Parental U-87 MG cells demonstrated limited dispersal in this assay. However,
PTPmu shRNA induced migration and dispersal of U-87 MG cells in the brain slice. Finally, in a mouse xenograft model of intracranially injected U-87 MG cells,
PTPmu shRNA induced morphological heterogeneity in these xenografts. Together, these data suggest that loss of
PTPmu in human GBMs contributes to
tumor cell migration and dispersal, implicating loss of
PTPmu in
glioma progression.