Scientists from the Cheeloo College of Medicine, Shandong University, Jinan, China, have discovered a link between androgens and stem cells that could contribute to colon cancer. It is known that colon cancers have a higher incidence in males, which is in part related to much higher androgen levels in males compared to females. Some cancers in the intestine are thought to arise from intestinal epithelial stem cells, which are needed for normal tissue maintenance and regeneration, but which can give rise to cancers when they grow improperly.
The research, ‘Androgen Maintains Intestinal Homeostasis by Inhibiting BMP Signaling via Intestinal Stromal Cells’, published in Stem Cell Reports, Drs Jingxin Li, Dawei Chen and colleagues found that androgen levels can regulate intestinal stem cell proliferation, a new potential link between androgen levels and colon cancer.
By tuning androgen levels in mice with genetic or pharmacological tools, the researchers found that high androgen levels cause intestinal stem cells to divide more than usual and at the same time generated less mature epithelial cells, characteristic of changes that can lead to tumour formation.
Interestingly, findings show that this effect was not direct but involved the surrounding niche cells, a population of cells that regulate intestinal stem cell growth and function. While important follow up research is needed, these findings may have implications for treating or preventing colon cancers through androgen regulation.
“According to our results, androgens bind to androgen receptor located in the mesenchyme and cause changes in the intestinal stem cell niche mediated by the mesenchyme,” the researchers concluded. The generation of inhibitors of canonical Wnt signalling was downregulated, leading to enhancement of Wnt/β-catenin signalling in ISCs. TGF-β1 and Bmp4 from mesenchyme were downregulated, and inhibitors of the BMP pathway were increased, causing reduced Bmp4/Id1/Msx1 and Tgfβ1/Cdkn1a/Cdkn2a/Cdkn2b signalling in ISCs.
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