Mice at risk of asthma, allergies can fight off skin cancer
A molecule involved in asthma and allergies has now been shown to make mice resistant to skin cancer, according to scientists at Washington University School of Medicine in St. Louis.
The molecule, called TSLP (thymic stromal lymphopoietin), is produced by damaged skin and activates the immune system. Chronic low levels of TSLP are suspected in making the immune system oversensitive to what should be a harmless environment, leading to the skin rashes and overproduction of mucus common in allergies and asthma.
"But at extremely high levels, TSLP appears to train the immune system to recognize skin cancer cells, and target those cells for elimination," says Raphael Kopan, PhD, the Alan A. and Edith L. Wolff Professor of Developmental Biology. "These experiments demonstrate that there is a way for a natural molecule to help immune cells recognize and reject tumors, at least in the skin."
The study appears online Oct 15 in Cancer Cell.
The disparity may be explained by the amount of TSLP that is produced. The mice that were resistant to skin tumor growth had blood levels of TSLP that were 1,000-fold higher than normal. And levels in the skin—where it is made—may be even higher.
"This is an example of where hyper-vigilance of the immune system may end up paying dividends," Kopan says. "Not only does it respond aggressively to an innocuous allergen, but it begins to monitor, survey and destroy cells that are mutant."
The results are supported by another study in the same issue of Cancer Cell also showing TSLP prevents skin cancer in mice.
For Kopan's group, the new research is the culmination of work that began more than six years ago. He and then graduate student Shadmehr Demehri, MD, PhD, wanted to investigate the defects found in mice born without a certain signaling protein in the skin. The protein, called Notch, is vital in properly forming many of the body's tissues, including skin.
Kopan calls it wonderful detective work, beginning with linking TSLP produced in the Notch-deficient skin with asthma. That study was published in PLoS Biology in 2009. And though they couldn't explain it at the time, they saw that many of these animals appeared to be immune to skin cancer.
"We were just trying to understand what was going on with our mice," Kopan says. "We did not set out to find a way to stimulate the immune system to eradicate tumors. But it's often the unexpected observations that lead to practical outcomes."
Since the mice expressed elevated levels of TSLP for genetic reasons related to abnormal Notch signaling, Kopan, Demehri and their colleagues asked whether TSLP would likewise protect normal mice from skin cancer. They tested a drug called Calcipotriol that dermatologists prescribe to treat psoriasis. Calcipotriol is considered a vitamin D "mimic" and is known to cause the skin to produce TSLP.
The researchers found that applying Calcipotriol to the skin of normal, healthy mice protected them from developing skin tumors when exposed to cancer-causing agents. In addition, they saw that existing skin tumors in otherwise normal mice shrank when Calcipotriol was applied.
"We already have treatments in clinical practice, often for other conditions, that induce the skin to produce TSLP," says Demehri, now a dermatology resident who treats patients at Barnes-Jewish Hospital. "So the next step is to find out if these topical drugs will be helpful in treating pre-cancerous skin lesions in humans."
Kopan stresses that more work must be done to fully understand the role of TSLP in skin cancer. In particular, these short-term studies were limited to the skin of mice and could not completely explain why Calcipotriol protected the healthy mice from skin cancer.
"In the Calcipotriol experiments, we have not fully separated whether the drug's beneficial effects are due to the production of TSLP, or the fact that the drug mimics vitamin D," Kopan says.
According to Kopan, future studies will also investigate whether TSLP might have similar effects on other types of cancer.
More information: Demehri S, Turkoz A, Manivasagam S, Yockey LJ, Turkoz M, Kopan R. Elevated epidermal thymic stromal lymphopoietin levels establish an anti-tumor environment in the skin. Cancer Cell. Online Oct. 15, 2012.
Di Piazza M, Nowell C, Koch U, Durham A-D, Radtke F. Loss of cutaneous TSLP dependent immune responses skews the balance of inflammation from tumor-protective to tumor-promoting. Cancer Cell. Online Oct. 15, 2012.
Demehri S, Morimoto M, Holtzman MJ, Kopan R. Skin-derived TSLP triggers progression from epidermal-barrier defects to asthma. PLoS Biology. May 19, 2009.
Provided by Washington University School of Medicine
- Skin defects set off alarm with widespread and potentially harmful effects May 28, 2008 | not rated yet | 0
- Why does eczema often lead to asthma? May 19, 2009 | not rated yet | 0
- Mice with skin condition help scientists understand tumor growth Jul 06, 2009 | not rated yet | 0
- Protein fuels inflammation in pancreatic and breast tumors Feb 21, 2011 | not rated yet | 0
- Researchers identify a target that could combat allergies of early childhood Aug 14, 2011 | 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
18 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 7 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 8 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 8 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 10 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 12 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 ...
14 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. ...
12 hours ago | 4.9 / 5 (10) | 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.
7 hours ago | 3 / 5 (2) | 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 ...
8 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.
14 hours ago | 4.5 / 5 (6) | 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.
9 hours ago | 5 / 5 (1) | 0 |