A luminal stem cell might fuel cancer
A new prostate stem cell found in mice might explain why prostate cancer often becomes resistant to standard therapies. Researchers led by Michael Shen of Columbia University in New York found that stem cells in the lumen of the prostate may be the ones that give rise to cancer. This contrasts with previously held assumptions that tumours arise from cells in the so-called basal layer. Importantly, these luminal cells do not require male sex hormones for survival, a characteristic they share with many late-stage prostate cancers.
The researchers knew that the gene Nkx3.1 regulates the differentiation of prostate epithelium and that its expression wanes both when androgens are absent and when tumours start to form. They were intrigued by a small population of cells expressing Nkx3.1 that persists even when the rest of the prostate regresses. The researchers characterized these cells and named them castration-resistant Nkx3.1-expressing (CARN) cells. Further work showed that these cells, which comprise less than 1% of all cells in the prostate, never express a key basal cell marker. A series of cell-labelling experiments showed that the CARN cell population expands as the prostate regenerates and that individual cells could generate ducts secreting prostate-specific proteins1. (Unrelated work has also identified a separate population of basal stem cells that can also reconstitute ducts in mice2.)
After characterizing the CARN cells, Shen and colleagues assessed whether the cells might cause cancer by disabling a gene called PTEN , which is known to suppress tumours. Mice with CARN cells lacking PTEN quickly developed carcinomas, whereas mice with functional PTEN in CARN cells did not.
Although cancer stem cells need not arise from normal stem cells, evidence suggests that intestinal cancer and breast cancer originate from tissue stem cells or progenitor cells. Such information could help scientists develop new drugs as well as strategies to prevent recurrence.
Shen and colleagues are now working to see whether CARN cells can be identified in human tissue and, if so, whether the cells seem likely to be cancer progenitors.
Wang, X. et al. MA luminal epithelial stem cell that is a cell of origin for prostate cancer. Nature , advance online publication (2008) 10.1038/nature08361
Leong, K.G., Wang, B-E., Johnson, L. & Gao, W-Q. Generation of a prostate from a single adult stem cell. Nature 456, 804–808 (2009).
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Baker, M. Prostate tumours from a surprising source. Nat Rep Stem Cells (2009). https://doi.org/10.1038/stemcells.2009.127