Source: Stanford School of Medicine – Krista Conger.
A single type of cell in the lining of the bladder is responsible for most cases of invasive bladder cancer, according to researchers at the Stanford University School of Medicine.
Their study, conducted in mice, is the first to pinpoint the normal cell type that can give rise to invasive bladder cancers. It’s also the first to show that most bladder cancers and their associated precancerous lesions arise from just one cell, and explains why many human bladder cancers recur after therapy.
“We’ve learned that, at an intermediate stage during cancer progression, a single cancer stem cell and its progeny can quickly and completely replace the entire bladder lining,” said Philip Beachy, Professor of Biochemistry and of Developmental Biology. “All of these cells have already taken several steps along the path to becoming an aggressive tumour. Thus, even when invasive carcinomas are successfully removed through surgery, this corrupted lining remains in place and has a high probability of progression.”
Although the cancer stem cells, and the precancerous lesions they form in the bladder lining, universally express an important signalling protein called sonic hedgehog, the cells of subsequent invasive cancers invariably do not — a critical switch that appears vital for invasion and metastasis. This switch may explain certain confusing aspects of previous studies on the cellular origins of bladder cancer in humans. It also pinpoints a possible weak link in cancer progression that could be targeted by therapies.
“This could be a game changer in terms of therapeutic and diagnostic approaches,” said Michael Hsieh, Assistant Professor of Urology and a co-author of the study. “Until now, it’s not been clear whether bladder cancers arise as the result of cancerous mutations in many cells in the bladder lining as the result of ongoing exposure to toxins excreted in the urine, or if it’s due instead to a defect in one cell or cell type. If we can better understand how bladder cancers begin and progress, we may be able to target the cancer stem cell, or to find molecular markers to enable earlier diagnosis and disease monitoring.” Beachy is the senior author of the study, published online April 20 in Nature Cell Biology…read the full story.