Neuropilin-2: Novel Biomarker and Therapeutic Target for Aggressive Prostate Cancer
Abstract
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. Recently, we obtained rigorous genetic evidence implicating NRP2 in the formation of prostate tumors, and in the genesis and function of prostate cancer stem cells. 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. Recently, we generated a model of resistance to therapy that reinforces the importance of VEGF/NRP2 signaling to the function of prostate cancer stem cells and the approach of targeting this pathway for therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2014
- Accession Number
- ADA611823
Entities
People
- Arthur M Mercurio
Organizations
- University of Massachusetts Medical School