Microenvironment-Programmed Metastatic Prostate Cancer Stem Cells (mPCSCs)
Abstract
The main goal of this DOD IDEA project is to further elucidate how orthotropic microenvironment (in the prostate) regulates prostate cancer metastasis. In particular, we wish to understand the cells-of-origin for PCa metastases. Clinically, some PCa patients harbor indolent tumors that rarely or only slowly progress whereas other patients have aggressive primary tumors that quickly progress and disseminate. To this end, we implanted multiple GFP or RFP tagged PCa cells either ecotipically in the subcutis (s.c) or orthotropically in the dorsal prostate (DP) or anterior prostate (AP) of NOD/SCID mice and followed, in great details, how tumors regenerate and metastasize. In the past year, we have generated exhaustive data to convincingly demonstrate that the DP- or AP-implanted human PCa cells metastasize much more widely and extensively than s.c-implanted counterparts. We then uncovered the DP and s.c prostate tumors and performed comparative genome-wide transcriptome analysis, which revealed an upregulation of ~600 genes in the DP (i.e., metastasisprone) tumors that fall into distinct, very informative functional classes. One class of genes, about 50 (~8% of total), is well-known stem cell/CSC regulators and/or markers. Preliminary functional studies on some of the genes implicate their importance in regulating PCa metastasis and in conferring properties of metastatic PCSCs (mPCSCs). In the coming year, we plan to perform extensive metastasis assays
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2014
- Accession Number
- ADA613324
Entities
People
- Dean Tang
Organizations
- The University of Texas MD Anderson Cancer Center