Putting the Brakes on Bladder Cancer

Bladder cancer metastasis slowed with RhoGDI2

(RxWiki News) As with any malignancy, once bladder cancer starts to travel to other parts of the body, an individual's chances of outliving it are diminished. So, preventing that spread is a major objective of research.

A protein that's sort of like a siren - versican - has been shown to help cancer cells get set up in the lung. This research discovered that another protein - RhoGD12 - silences versican so that cancer cells can't grow and thrive in the lung.

"If your urine turns dark or rust colored, see your doctor."

The paper's senior author, Dan Theodorescu, M.D., Ph.D., director of the University of Colorado Cancer Center, says this finding could help people with bladder cancer live longer.

Metastasis isn't something that happens all of a sudden. Cells don't start moving just out of the blue.

No, these cells may have been stalking around in the blood or lymph for a while, just looking for a place to land, latch on and grow. 

The lungs are a great landing pad for cancer cells.

But getting settled in is stressful for these cells. They get overwhelmed and panicked. When that happens, they make a distress call, and versican responds to save the day and the cancer.

The more versican that builds up, the more support troops arrive in what's known as macrophages, which are sort of like garbage men. They eat up stuff that could a cell harm, even if that cell is a potential killer.

So the macrophages support the bladder cancer cells in getting set up in lungs and that's when metastasis takes hold and over.

The protein RhoGDI2 puts the brakes on this process, Dr. Theodorescu and colleagues demonstrated, by decreasing the levels of versican. When they added RhoGD12 to a bladder tumor in the lab, versican and metastasis were both decreased. 

"We believe this study provides an important contribution to the scientific literature by delineating for the first time a new mechanism of metastasis suppression, namely that suppression of metastasis is possible by altering the tumor microenvironment, including reducing the presence of macrophages," Theodorescu says.

The story doesn't end there. Another protein called CCL2 helps versican recruit macrophages. And that's a nifty finding because, clinical trials are already under way testing drugs that inhibit, or block CCL2.

If the laboratory results can be repeated in humans, these drugs might just be the ticket to lowering metastasis, thereby significantly extending lives.

When asked what all this means, Dr. Theodorescu told dailyRx, “The significance of our study to patients is that two of the drugs used have the very real possibility of crossing over quickly to human use. This could be a major advance in keeping bladder cancer from metastasizing to the lungs,” he concluded.

This study was published March 12, 2012 in the Journal of Clinical Investigation. 

The research was funded by the National Institutes of Health. No conflicts of interest were disclosed.

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Review Date: 
March 14, 2012