Distinct phases of human prostate cancer initiation and progression can be driven by different cell-types

Abstract

The cells that initiate and propagate cancer are important therapeutic targets. However, the progression from cells of origin to tumor-propagating cells is poorly defined for most human cancers. Mouse models indicate that both basal and luminal cells can initiate prostate cancer, while studies with human prostate tissue have demonstrated a role for basal cells in transformation. Our recent study provides evidence that a common cell of origin can produce alternative variants of human epithelial cancer. Our findings also reveal that the cell of origin that initiates cancer is not continuously required to maintain and propagate the disease. Importantly, the cells responsible for initiating human prostate cancer can have a distinct cellular phenotype from the cells needed to maintain it.

Keywords: basal-like cells; epithelial cells; prostate cancer; tumor-propagating cells.

Figure 1. Cell populations with distinct phenotypes can initiate and propagate human prostate cancer

Model of transformation of epithelial subsets (basal-CD49f^hi and luminal-CD49f^low) with Myc and myrAKT resulting in tumors from the basal fraction but not from the luminal population. CD49f^hi cells isolated from mixed tumors (containing both adenocarcinoma and squamous features) could propagate mixed tumors, while CD49f^loK18⁺ luminal-like tumor cells propagate strictly adenocarcinoma in the absence of CD49f^hi or K14+ p63+ basal-like cells.