Invasive prostate cancer cells are tumor initiating cells that have a stem cell-like genomic signature

• Published in: Clinical & experimental metastasis 2009, Vol.26 (5), p.433-446
• Main Authors: Klarmann, George J, Hurt, Elaine M, Mathews, Lesley A, Zhang, Xiaohu, Duhagon, Maria A, Mistree, Tashan, Thomas, Suneetha B, Farrar, William L
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Cancer Research; CD24 Antigen - biosynthesis; Epithelium - pathology; Genomics; Hematology; Humans; Hyaluronan Receptors - biosynthesis; Male; Mesoderm - metabolism; Mice; Mice, Inbred NOD; Mice, SCID; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplastic Stem Cells - metabolism; Oncology; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Research Paper; Stem Cells - metabolism; Surgical Oncology
• ISSN: 0262-0898; 1573-7276
• DOI: 10.1007/s10585-009-9242-2

Development of metastasis is a leading cause of cancer-induced death. Acquisition of an invasive tumor cell phenotype suggests loss of cell adhesion and basement membrane breakdown during a process termed epithelial-to-mesenchymal transition (EMT). Recently, cancer stem cells (CSC) were discovered to mediate solid tumor initiation and progression. Prostate CSCs are a subpopulation of CD44⁺ cells within the tumor that give rise to differentiated tumor cells and also self-renew. Using both primary and established prostate cancer cell lines, we tested the assumption that CSCs are more invasive. The ability of unsorted cells and CD44-positve and -negative subpopulations to undergo Matrigel invasion and EMT was evaluated, and the gene expression profiles of these cells were analyzed by microarray and a subset confirmed using QRT-PCR. Our data reveal that a subpopulation of CD44⁺ CSC-like cells invade Matrigel through an EMT, while in contrast, CD44⁻ cells are non-invasive. Furthermore, the genomic profile of the invasive cells closely resembles that of CD44⁺CD24⁻ prostate CSCs and shows evidence for increased Hedgehog signaling. Finally, invasive cells from DU145 and primary prostate cancer cells are more tumorigenic in NOD/SCID mice compared with non-invasive cells. Our data strongly suggest that basement membrane invasion, an early and necessary step in metastasis development, is mediated by these potential cancer stem cells.