Root cause of bladder cancer revealed, highlighted in Nature Reviews Urology

May 13, 2014

Bladder cancer cell of origin study (Shin, Beachy, NCB 2014) was highllighted in Nature Reviews Urology. Previous studies have shown that a population of sonic hedgehog (Shh)-expressing basal urothelium cells can propagate and regenerate all types of urothelial cells (Shin, Beachy Nature 2011), placing them as the likely candidates for bladder cancer stem cells.This work paved the way for us to examine the general idea that stem cells might give rise to cancers in the specific context of the bladder, and that is the subject of our current study. In original study, we used a mouse model of bladder cancer induced by the chemical carcinogen N-butyl-N-4- hydroxybutyl nitrosamine (BBN), which follows the same course as human disease. We performed two major experiments. First, they genetically marked the basal urothelial stem cells with GFP and found that all the resulting invasive tumours were also marked, implying that all muscle-invasive carcinomas are exclusively derived from these stem cells. Then, we ablated the stem cells and found that no tumours developed after BBN treatment, even when treatment was prolonged. In addition, we used a multi-colour fluorescent mouse—also known as the ‘Rainbow mouse’ —to precisely determine the clonality and cellular origin of bladder cancer. We found that the entire tumour, as well as surrounding premaligant lesions, was labelled with one colour, indicating that a single stem cell takes over the lining of the entire urothelium during cancer progression, leading to the formation of a tumour originating from a single cell.

 

 

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Shin Lab | Department of Life Sciences | Pohang University of Science and Technology