Prostate Sphere-forming Stem Cells Are Derived from the P63-expressing Basal Compartment. Academic Article uri icon

abstract

  • Prostate stem cells (P-SCs) are capable of giving rise to all three lineages of prostate epithelial cells, including basal, luminal, and neuroendocrine cells. Multiple methods have been used to identify P-SCs in adult prostates. These include in vivo renal capsule implantation of a single epithelial cell with urogenital mesenchymal cells, in vitro prostasphere and organoid cultures, and lineage tracing with castration-resistant Nkx3.1 expression (CARN), in conjunction with expression of cell type-specific markers. Both organoid culture and CARN tracing show the existence of P-SCs in the luminal compartment. Although prostasphere cells predominantly express basal cell-specific cytokeratin and P63, the lineage of prostasphere-forming cells in the P-SC hierarchy remains to be determined. Using lineage tracing with P63(CreERT2), we show here that the sphere-forming P-SCs are P63-expressing cells and reside in the basal compartment. Therefore we designate them as basal P-SCs (P-bSCs). P-bSCs are capable of differentiating into AR(+) and CK18(+) organoid cells, but organoid cells cannot form spheres. We also report that prostaspheres contain quiescent stem cells. Therefore, the results show that P-bSCs represent stem cells that are early in the hierarchy of overall prostate tissue stem cells. Understanding the contribution of the two types of P-SCs to prostate development and prostate cancer stem cells and how to manipulate them may open new avenues for control of prostate cancer progression and relapse.

published proceedings

  • J Biol Chem

altmetric score

  • 52.5

author list (cited authors)

  • Huang, Y., Hamana, T., Liu, J., Wang, C., An, L., You, P., ... Wang, F

citation count

  • 21

complete list of authors

  • Huang, Yanqing||Hamana, Tomoaki||Liu, Junchen||Wang, Cong||An, Lei||You, Pan||Chang, Julia YF||Xu, Jianming||McKeehan, Wallace L||Wang, Fen

publication date

  • July 2015