The
receptor protein tyrosine phosphatase beta (
RPTPbeta/PTPzeta) is overexpressed in
glioblastoma tumors and plays a functional role in
tumor cell migration and adhesion.
Glioblastomas express at least three splice variants of
RPTPbeta, including long and short receptor forms and a secreted
chondroitin sulfate proteoglycan called
phosphacan. Here we explore the differences in the expression pattern and function of long
RPTPbeta and short
RPTPbeta. The short form of
RPTPbeta lacks exon 12, which encodes 860
amino acids located in the extracellular domain. Until now, functional differences between long and short
RPTPbeta have been difficult to elucidate. In this study,
antibodies specific to the splice junction, unique to short
RPTPbeta, allowed for the discrimination of the two receptors. A study of normal brain tissue and graded
astrocytomas indicates that long and short
RPTPbeta forms have an overlapping expression pattern. In order to study functional differences between long and short
RPTPbeta, we created stable U87
glioblastoma cells that expressed these receptors. U87 stable cell lines overexpressing long or short
RPTPbeta migrate faster and adhere more robustly than parental U87 cells. The two forms differ in that long-
RPTPbeta-overexpressing cells migrate and adhere better than short-
RPTPbeta-overexpressing cells. A study of the extracellular domain of short
RPTPbeta indicates that it retains much of the functional capacity of
phosphacan. Indeed, the action of recombinant, short-
RPTPbeta extracellular domain protein is similar to that of
phosphacan as a repulsive substrate for
glioblastoma cells. Comparison of the signaling capacity of long
RPTPbeta to that of short
RPTPbeta reveals very similar abilities to activate transcription pathways. Moreover, transient transfection with either long or short
RPTPbeta activates
NF-kappaB reporter gene transcription. Because of their
tumor-restricted and largely overlapping expression patterns in
glioblastoma, both
RPTPbeta splice forms are potential therapeutic targets. The involvement of long and short
RPTPbeta in
glioma tumor cell biology also contributes to the value of
RPTPbeta as a
cancer target.