Prostate Stem Cells and Cancer Stem Cells

Abstract

Stem/progenitor cells play central roles in processes of organogenesis and tissue maintenance, whereas cancer stem cells (CSCs) are thought to drive tumor malignancy. Here, we review recent progress in the identification and analysis of normal prostate stem/progenitor cells as well as putative CSCs in both genetically engineered mouse models as well as in human tissue. We also discuss studies that have investigated the cell type of origin for prostate cancer. In addition, we provide a critical assessment of methodologies used in stem cell analyses and outline directions for future research.

Figure 1.

Lineage hierarchy and cell types of origin for cancer. Schematic representation of simple lineage hierarchy within an epithelial tissue. Distinct normal cell types arise from a stem cell that is capable of self-renewal and multipotency, under the influence of a stem cell niche. Different tumor subtypes may arise from oncogenic transformation of the stem cell or non–stem cells within the lineage hierarchy. (From Shibata and Shen 2013; adapted, with permission, from the authors.)

Figure 2.

Different types of functional assays for prostate stem cells and cancer stem cells. (Left) In cell culture assays, dissociated cells from normal prostate tissue or prostate tumors can be examined for their ability to form colonies in two-dimensional (2D) culture or to form organoids in three-dimensional (3D) culture. In xenografting assays, dissociated tumor cells can be grafted subcutaneously or orthotopically. Alternatively, tissue reconstitution using dissociated normal or tumor cells involves recombination with embryonic urogenital sinus mesenchyme (UGSM) followed by grafting under the renal capsule. (Right) Lineage tracing in genetically engineered mouse (GEM) models involves the creation of a genetic lineage mark, often using inducible Cre recombinase, followed by analysis of marked tissue (indicated in green) to ascertain lineage relationships. (From Shibata and Shen 2015; adapted, with permission, from the authors.)