Genomic Analysis of Prostate Cancer Stem Cells Isolated from a Highly Metastatic Cell Line

Abstract

Background: Tumor-initiating or cancer stem cells (CSCs) were recently isolated from all major human cancers, including prostate cancer. However, the extreme heterogeneity of tumor cells in terms of biological behavior and gene expression patterns and difficulties isolating a pure population of CSCs from tumor tissues significantly impede a comparative analysis of CSCs. Materials and Methods: Different phenotypic populations were isolated from a metastatic derivative of PC-3 cell line, PC3-MM2, and tested for their ability to form tumors in NOD/SCID mice and floating spheroids in 3D culture systems. Results: All tested cell lines possessed minor populations of cells with highest expression of CD133, CD44 and CD166, whereas the vast majority of cells were CD133-negative. Several experimental approaches promoted a higher proportion of CD133-positive cells with increased in vivo tumorigenicity and the ability to produce floating spheres. Genome-wide microarray analysis (Affymetrix; DAVID) of CSC-enriched versus CSC-depleted cell populations revealed 213 genes with 10-100 fold increased activity out of 8994 differentially expressed ones and 87 genes with 5-50 fold decreased activity. Conclusions: The proposed in vitro prostate CSC model allows for reliable isolation and propagation of highly tumorigenic cells. This study may contribute to the identification of novel targets for CSC-targeted prostate cancer treatment.