Accession Number : AD1024131


Title :   Understanding and Targeting Tumor Microenvironment in Prostate Cancer to Inhibit Tumor Progression and Castration Resistance


Descriptive Note : Technical Report,30 Sep 2015,29 Sep 2016


Corporate Author : MD Anderson Cancer Center Houston United States


Personal Author(s) : Lu,Xin


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1024131.pdf


Report Date : 01 Oct 2016


Pagination or Media Count : 30


Abstract : The signaling mechanisms between prostate cancer cells and infiltrating immune cells may illuminate novel therapeutic approaches. In Year2, utilizing a prostate adenocarcinoma model driven by loss of Pten and Smad4, I further validated that polymorphonuclear myeloid-derived suppressor cells (MDSCs) are the major infiltrating immune cell type and depletion of MDSCs blocks progression. Employing a novel dual reporter prostate cancer model, epithelial and stromal transcriptomic profiling identified Cxcl5 as a cancer-secreted chemokine to attractCxcr2-expressing MDSCs and, correspondingly, pharmacological inhibition of Cxcr2 impeded tumor progression. Integrated analyses identified hyperactivated Hippo-YAP signaling in driving Cxcl5 upregulation in cancer cells through YAP-TEAD complex and promoting MDSCs recruitment. Clinico-pathological studies reveal upregulation and activation of YAP1 in a subset of human prostate tumors, and theYAP1 signature is enriched in primary prostate tumor samples with stronger expression of MDSC relevant genes. Together, YAP-driven MDSC recruitment via heterotypic Cxcl5-Cxcr2 signaling reveals effective therapeutic strategy for advanced prostate cancer.


Descriptors :   prostate cancer , metastasis , therapeutics , cancer research , inhibitors , epithelial cells , stromal cells , microarray analysis , myeloid cells , neoplasms


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE