Protein tyrosine phosphatase mu regulates glioblastoma cell growth and survival in vivo

Glioblastoma multiforme (GBM) is the most lethal primary brain tumor. Extensive proliferation and dispersal of GBM tumor cells within the brain limits patient survival to approximately 1 year. Hence, there is a great need for the development of better means to treat GBM. Receptor protein tyrosine phosphatase (PTP)μ is proteolytically cleaved in GBM to yield fragments that promote dispersal of GBM cells. While normal brain tissue retains expression of full-length PTPμ, low-grade human astrocytoma samples have varying amounts of full-length PTPμ and cleaved PTPμ. In the highest-grade astrocytomas (i.e., GBM), PTPμ is completely proteolyzed into fragments. We demonstrate that short hairpin RNA mediated knockdown of full-length PTPμ and PTPμ fragments reduces glioma cell growth and survival in vitro. The reduction in growth and survival following PTPμ knockdown is enhanced when cells are grown in the absence of serum, suggesting that PTP may regulate autocrine signaling. Furthermore, we show for the first time that reduction of PTP protein expression decreases the growth and survival of glioma cells in vivo using mouse xenograft flank and i.c. tumor models. Inhibitors of PTPμ could be used to reduce the growth and survival of GBM cells in the brain, representing a promising therapeutic target for GBM.