Major study stops bladder cancer from metastasizing to lungs
The diagnosis of localized bladder cancer carries an 80 percent five-year survival rate, but once the cancer spreads, the survival rate at even three years is only 20 percent. A major study published today in the Journal of Clinical Investigation not only shows how bladder cancer metastasizes to the lungs but pinpoints a method for stopping this spread.
Specifically, the study shows that versican, a protein involved in cancer cell migration, is a driver of lung metastasis and that high levels of versican are associated with poor prognosis in bladder cancer patients. The study is the first to show how that when a cancer cell makes the protein RhoGDI2, it reduces the cell's production of versican, thus blocking the ability of the cancer cell to grow in the lungs.
"For a decade, we've known that the major challenge of treating bladder cancer is treating or preventing the metastatic form of the disease. This study represents an advance in the latter by preventing the spread of bladder cancer to the lungs, we could improve patient survival," says Dan Theodorescu, MD, PhD, director of the University of Colorado Cancer Center, the paper's senior author.
When a cancer metastasizes from its birth location to another, it's not necessarily that cells suddenly become mobile and thus able to float through the blood or lymph to new homes. In fact, these cancer cells may have been floating through a patient's blood for quite some time, and metastasis occurs only when one of these intrepid cells is finally able to grow in the place where it is attached, such as the lungs.
When the first cancer cells to attach to, say, the lung, they have a tough time they become distressed. Cancer cells express this distress in the form of versican. And the more versican they express, the more help they get, which arrives in the form of macrophages, a part of the body's immune response that eat pathogens and other debris.
In most cases, the fact that macrophages benefit distressed cells is good, but in addition to helping healthy cells survive, these arriving macrophages also promote the growth of cancer cells that have landed in distant sites such as the lung, thus promoting metastasis of the disease.
More versican made by the cancer cells calls more macrophages, which aid cancer cells' survival and increase the likelihood that a cancer cell's toehold will develop into a clinically significant tumor in the lung.
Theodorescu and colleagues showed that the protein RhoGDI2 reduces the expression of versican. Cancer cells that make more RhoDI2 produce less versican and thus call fewer macrophages, making it difficult for these high-RhoGDI2 cancer cells to survive.
Sure enough, when Theodorescu and colleagues added RhoGDI2 to tumors, versican went down and with it so did metastasis.
"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 macrophages," Theodorescu says.
In fact, this paper also shows for the first time one more step: versican's ability to attract macrophages to the tumor depends on a protein called CCL2. This step is important because drugs that inhibit CCL2 are already in clinical trials for other conditions.
If the effect in humans is the same as the effect in the laboratory namely that inhibiting CCL2 reduces versican's ability to attract the macrophages that promote tumor growth at distant sites one of these CCL2 inhibitors could soon become part of the treatment regimen for bladder cancer patients with tumors that make low levels of RhoGDI2 and high versican. This approach has the potential to lower the chance of bladder cancer metastasis and thus a significantly improved outcome for patients with high risk bladder cancer.
Journal reference: Journal of Clinical Investigation
Provided by University of Colorado Denver
- Lung cancer cells activate inflammation to induce metastasis Dec 31, 2008 | not rated yet | 0
- Some cancer drugs may block cellular 'cross talk' but not kill cancer cells Dec 22, 2010 | not rated yet | 0
- Researchers reveal how cancer cells change once they spread to distant organs Feb 22, 2012 | not rated yet | 0
- Crucial molecule that involved in spread of breast cancer found Jun 08, 2011 | not rated yet | 0
- New discovery raises doubts about current bladder treatment Mar 25, 2009 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
How can there be a term called "intestinal metaplasia" of stomach
17 hours ago Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
- More from Physics Forums - Medical Sciences
More news stories
The gap between life expectancy in patients with a mental illness and the general population has widened since 1985 and efforts to reduce this gap should focus on improving physical health, suggest researchers in a paper ...
Cancer 5 hours ago | not rated yet | 0
By studying the roles two proteins, thrombospondin-1 and prosaposin, play in discouraging cancer metastasis, a trans-Atlantic research team has identified a five-amino acid fragment of prosaposin that significantly reduces ...
Cancer 6 hours ago | not rated yet | 0
A novel transcriptome-based classification of colon cancer that improves the current disease stratification based on clinicopathological variables and common DNA markers is presented in a study published in PLOS Medicine this w ...
Cancer 7 hours ago | not rated yet | 0
A study of veterans at high risk for developing lung cancer shows that low-dose computed tomography (LDCT) can be highly effective in helping clinicians spot tiny lung nodules which, in a small number of patients, may indicate ...
Cancer 8 hours ago | not rated yet | 0
An attack on glioblastoma brain tumor cells that uses a modified poliovirus is showing encouraging results in an early study to establish the proper dose level, researchers at Duke Cancer Institute report.
Cancer 10 hours ago | not rated yet | 0
(Medical Xpress)—Native peoples in regions where cameras are uncommon sometimes react with caution when their picture is taken. The fear that something must have been stolen from them to create the photo ...
12 hours ago | 4.2 / 5 (5) | 0 |
(Medical Xpress)—Despite spending billions of dollars on research and development, drug companies have been unable to come up with effective treatments for dementia and Alzheimer's Disease (AD). Now, A. ...
10 hours ago | 4.9 / 5 (9) | 0 |
Activating an enzyme known to play a role in the anti-aging benefits of calorie restriction delays the loss of brain cells and preserves cognitive function in mice, according to a study published in the May ...
7 hours ago | 5 / 5 (3) | 0 |
Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes.
12 hours ago | 4.5 / 5 (6) | 0 |
An experimental sleeping pill from US drug company Merck is effective at helping people fall and stay asleep, according to reviewers at the US Food and Drug Administration, which could soon approve the new drug.
6 hours ago | 3 / 5 (2) | 0
A drug commonly used to treat depression and anxiety may improve a stress-related heart condition in people with stable coronary heart disease, according to researchers at Duke Medicine.
8 hours ago | 5 / 5 (1) | 0 |