Scientists Show Protein Key To Bladder Cancer Spread, Potential Drug Target

"The fact that proepithelin doesn't appear to strongly promote cell proliferation, but instead promotes migration and invasion – two crucial steps leading to metastasis – suggests that it could be critical for the passage of a cancer from a noninvasive to an invasive phenotype," says Andrea Morrione, Ph.D., research assistant professor of urology at Jefferson Medical College of Thomas Jefferson University and Jefferson's Kimmel Cancer Center in Philadelphia.

In some cases, he notes, proepithelin might be used as a marker for bladder cancer. He and his colleagues report their findings July 15, 2006 in the journal Cancer Research.

Proepithelin is found in higher-than-normal levels in breast, ovarian and renal cancers, in addition to deadly brain cancers known as glioblastomas. It plays important roles in development, cell movement and tumor formation.

The American Cancer Society estimates that 61,420 new cases of bladder cancer will be found in the United States during 2006, making it the fifth most common cancer in this country. About 13,060 people will die of the disease. While it is treatable, especially if caught early, the cancer often returns and spreads to other areas of the body, and little is known about the molecular mechanisms behind its formation.

Dr. Morrione, along with a team including Renato Iozzo, M.D., professor of pathology, anatomy and cell biology, Raffaele Baffa, M.D., associate professor of urology, and Leonard Gomella, M.D., professor and chair of urology, all at Jefferson Medical College, knew that proepithelin was important in cell migration and wanted to investigate its potential role in bladder tumor formation.

In the study, using 5637 bladder cancer cells (cells from a type of bladder cancer), the group showed that proepithelin promoted migration of the bladder cancer cells and stimulated wound closure and invasion. He notes that looking at wound healing – "the ability of the cells to migrate and close gaps" – was another technique used to confirm proepithelin's role.

When they looked more closely at the molecular pathways involved in bladder cancer formation, they discovered that proepithelin turned on a common pathway called MAP kinase. Dr. Morrione believes that proepithelin will be found to have similar roles in other cancers.

He notes that one next step in the work is to verify whether or not proepithelin could be a marker in bladder tumors to use to predict metastasis. Bladder tumors are sometimes difficult to treat because of recurrence, he says. "There is a need for a non-invasive test for early detection of bladder tumors."