AMC unravels clues in treating relapsing, metastatic bladder cancer

Lee Han-soo  Published 2019.12.06  18:22  Updated 2019.12.06 18:22


Asan Medical Center researchers have clarified the pathogenesis of cancer stem cells that develop into bladder cancer and found evidence to treat bladder cancer.

Bladder cancer is the fourth most common malignant tumor in men, and the incidence rate is steadily increasing in Korea due to Westernized eating habits, environmental pollution, and aging. It is also the most expensive cancer to treat due to the high recurrence after treatment, which, in turn, leads to a lifetime of cancer recurrence screening and periodical treatment.

Professors Shin Dong-myung (left) and Cho Young-mi

Besides, 75 percent of bladder cancers are superficial bladder cancers that are more likely to recur and become more advanced with advanced bladder cancers. The survival rate is known to be only 5 percent.

The team, led by Professors Shin Dong-myung and Cho Young-mi, discovered a mechanism by which stem cell-specific proteins, cyclin-dependent kinase 1 (CDK1), and transcription factor CP2 like 1 (TFCP2L1), cause bladder cancer stem cell growth, which develops into bladder cancer.

The researchers also found that bladder cancer stem cells eventually influenced the malignancy of bladder cancer, metastasis to lymph nodes and other organs, and patient mortality, demonstrating a close association with poor prognosis of bladder cancer.

In detail, the team first discovered that TFCP2L1 plays a vital role in stem cell regulation of embryonic and adult stem cells.

Also, they confirmed that CDK1, an essential protein for cell division, phosphorylates TFCP2L1 protein directly, thereby enhancing stem cell and cell cycle-related gene expression, and inhibiting cell differentiation gene expression.

Based on these findings, overexpression of CDK1 and TFCP2L1 and phosphorylation of TFCP2L1 were confirmed by immunohistochemically staining in 400 bladder cancer tissues.

The results showed that bladder cancer affects the malignancy, muscle invasiveness, lymph node metastasis, and metastasis to other organs and is closely related to the increase patient mortality.

The team also reconfirmed their results against the U.S. National Institutes of Health data.

“Although bladder cancer stem cells have been suggested as a major cause of high recurrence rate and resistance to chemotherapy, the exact mechanism of bladder cancer stem cells have not been identified,” the team said. “However, this study reveals stem cell mechanisms, which will increase the possibility of developing targeted therapies and become a new turning point in the treatment of refractory bladder cancer.”

Professor Shin also said, “As the importance of stem cell proliferation is suggested as the most notable theory explaining the high recurrence rate of bladder cancer and resistance after chemotherapy, this study is expected to develop new bladder cancer therapies targeting bladder cancer stem cell characteristics.”

Embo Molecular Medicine published the results of the study.

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