Featured Research

from universities, journals, and other organizations

Mice at risk of asthma, allergies can fight off skin cancer

Date:
October 15, 2012
Source:
Washington University in St. Louis
Summary:
A molecule involved in asthma and allergies has now been shown to make mice resistant to skin cancer, according to scientists.

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.

Related Articles


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.

These findings are surprising because most current evidence suggests that the allergic inflammation and release of TSLP increases -- not decreases -- the risk of tumor development.

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.


Story Source:

The above story is based on materials provided by Washington University in St. Louis. Note: Materials may be edited for content and length.


Journal References:

  1. Shadmehr Demehri, Ahu Turkoz, Sindhu Manivasagam, Laura J. Yockey, Mustafa Turkoz, Raphael Kopan. Elevated Epidermal Thymic Stromal Lymphopoietin Levels Establish an Antitumor Environment in the Skin. Cancer Cell, 2012; 22 (4): 494%u2013505 DOI: 10.1016/j.ccr.2012.08.017
  2. Matteo Di Piazza, Craig S. Nowell, Ute Koch, Andrι-Dante Durham, Freddy Radtke. Loss of Cutaneous TSLP-Dependent Immune Responses Skews the Balance of Inflammation from Tumor Protective to Tumor Promoting. Cancer Cell, 2012; 22 (4): 479%u2013493 DOI: 10.1016/j.ccr.2012.08.016
  3. Shadmehr Demehri, Mitsuru Morimoto, Michael J. Holtzman, Raphael Kopan. Skin-Derived TSLP Triggers Progression from Epidermal-Barrier Defects to Asthma. PLoS Biology, 2009; 7 (5): e1000067 DOI: 10.1371/journal.pbio.1000067

Cite This Page:

Washington University in St. Louis. "Mice at risk of asthma, allergies can fight off skin cancer." ScienceDaily. ScienceDaily, 15 October 2012. <www.sciencedaily.com/releases/2012/10/121015121734.htm>.
Washington University in St. Louis. (2012, October 15). Mice at risk of asthma, allergies can fight off skin cancer. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2012/10/121015121734.htm
Washington University in St. Louis. "Mice at risk of asthma, allergies can fight off skin cancer." ScienceDaily. www.sciencedaily.com/releases/2012/10/121015121734.htm (accessed November 28, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, November 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Experimental Ebola Vaccine Shows Promise In Human Trial

Experimental Ebola Vaccine Shows Promise In Human Trial

Newsy (Nov. 27, 2014) — A recent test of a prototype Ebola vaccine generated an immune response to the disease in subjects. Video provided by Newsy
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) — Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) — Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins