Neuropilin-2: Novel Biomarker and Therapeutic Target for Aggressive Prostate Cancer

The focus of this proposal is Neuropilin-2 (NRP2), a VEGF receptor that is not expressed in normal prostate but is expressed in prostate cancer and correlates with Gleason grade. We demonstrated that PTEN deletion induces NRP2 expression and propose that NRP2 contributes to the function of prostate cancer stem cells and tumor formation. We also discovered that NRP2 facilitates the expression of Bmi-1, a transcriptional repressor, and that NRP2 suppresses the IGF-1 receptor (IGF-1R) by a mechanism that involves transcriptional repression by Bmi-1. We have obtained preliminary evidence that targeting NRP2 directly on tumor cells in combination with IGF-1R inhibition is effective treating aggressive prostate carcinoma and pursuing this possibility more rigorously. The role of VEGF/NRP2 signaling in the function of prostate cancer stem cells and tumor initiation is also being investigated.
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