New research shows that most cases of bladder cancer may be driven by a single cell type, illuminating a possible therapy target for the disease that kills thousands of Americans each year.
Dr. Philip Beachy, a researcher at Stanford University School of Medicine and senior author of the new study, said the results point to a certain stem cell that occurs in the lining of the bladder. Aside from providing a new factor of care and diagnosis, the discovery helps explain why invasive bladder cancers tend to return after treatment.
"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," he explained in a press release. "All of these cells have already taken several steps along the path to becoming an aggressive tumor. Thus, even when invasive carcinomas are successfully removed through surgery, this corrupted lining remains in place and has a high probability of progression."
To investigate, the researchers conducted experiments with two mouse models of bladder cancer. In the first model, they marked the stem cell type with a distinctive fluorescent color. In the second, they selectively killed the cell type before exposing subjects to carcinogenic chemicals.
The results, published in the journal Nature Cell Biology, provide strong evidence that the cell type plays a key role in invasive bladder cancer. In their first mouse model, they found that nearly the entire bladder lining shone green. According to Beachy, this means that most cancerous tissue arose from the marked stem cell.
Conversely, the second model exhibited no tumor growth at all, despite continued exposure to carcinogens. "So now we have two lines of evidence indicating that the bladder stem cells are solely responsible for tumorigenesis," said Dr. Kunyoo Shin, an instructor at the Howard Hughes Medical Institute and lead author of the study. "When we mark the bladder stem cells, the tumors are also marked. When we remove, or ablate, the stem cells, no tumors arise.”
According to the American Cancer Society, bladder cancer currently affects 74,690 Americans each year, with about 15,000 annual deaths. It is the fourth most common cancer in men, and the ninth most common in women. While the majority of cases remain confined to the bladder lining, about a third of all cases are invasive, meaning they invade muscle around the bladder and metastasize to neighboring organs.
Source: Shin K, Lim A, Odegaard JI, et al. Cellular origin of bladder neoplasia and tissue dynamics of its progression to invasive carcinoma. Nature Cell Biology. 2014.