Featured Research

from universities, journals, and other organizations

Mice With Skin Condition Help Scientists Understand Tumor Growth

Date:
July 9, 2009
Source:
Washington University School of Medicine
Summary:
Cancerous tumors sometimes form at the site of chronic wounds or injury, but the reason why is not entirely clear. Now researchers have engineered mice with a persistent wound-like skin condition, and the mice are helping them understand the tumor-promoting effects of long-standing wounds and injuries.

Cancerous tumors sometimes form at the site of chronic wounds or injury, but the reason why is not entirely clear. Now researchers at Washington University School of Medicine in St. Louis have engineered mice with a persistent wound-like skin condition, and the mice are helping them understand the tumor-promoting effects of long-standing wounds and injuries.

Related Articles


"The chronic skin condition in the mice led to the growth of skin tumors," says Raphael Kopan, Ph.D., professor of developmental biology and of dermatology. "And what we learned from this process fit very well with the emerging realization that a tumor's surroundings play a critical role in its development."

Past clinical evidence has linked chronic skin wounds such as leg ulcers to an increased risk of skin cancer, and some scientists have suggested that chronic injury can predispose various organs to cancer.

In this study, published in Cancer Cell, the researchers found that the chronic skin condition led to secretion of molecules that activated dermal cells, increased the number of blood vessels and increased local inflammation, reinforcing the idea that wound repair mechanisms and inflammation are important agents in promoting cancer. The skin condition was engineered in the mice by inactivating a gene called Notch1 in patches of skin cells, leaving the rest of the skin intact. Notch1 is a master controller for normal skin development and was thought to suppress tumor growth in skin cells in which it resides.

Without Notch1, patches of the mice's skin developed abnormally and became thickened and inflamed. As the mice aged, benign tumors called papillomas formed. About 10 percent of these tumors spontaneously progressed to basal cell carcinoma, the most common type of skin cancer in people.

Importantly, further analysis showed that skin tumors had originated from both mutant and normal skin cells. Because normal cells contain active Notch1, they were not expected to form tumors, and that was an important clue that factors other than the missing Notch1 were responsible for tumor formation in skin.

"Loss of Notch1 signaling in the mutant skin cells generated a wound-like environment in which both the mutant and normal skin cells became prone to cancer," Kopan says.

The research team showed that the mutant skin patches encouraged the growth of tiny blood vessels and production of growth factors that when expressed transiently help repair skin damage. The persistent expression of these factors provided cells with nutrients and proliferation signals that promoted tumor formation, Kopan says. Numerous immune cells secreting additional factors infiltrated the abnormal skin patches and adjacent cells, contributing to inflammation.

Recently, drugs that lower Notch1 activity have been used to manage Alzheimer's disease and to treat some forms of cancer – because paradoxically Notch1 can be a tumor promoter in tissues other than skin. Kopan says that his study shows that skin is very sensitive to reduction of Notch1 activity. The long-term use of such medications and others that compromise skin integrity could contribute to an increased likelihood of skin cancer, he says.

"The study suggests that as researchers develop drugs, they should be mindful of their potential effect on the skin, particularly those that cause chronic damage to skin integrity," Kopan says. "Studies like ours help define the range of possible complications in drug design and help tailor therapies to avoid them."

The researchers also plan to use Notch-deficient mice to provide a system in which to identify molecules and cellular interactions responsible for the oncogenic effect of chronic wounds. Based on such analyses, new drug targets might be identified to develop therapies for cancers of the skin and perhaps other organs.

"It's very reasonable to assume that chronic wounds in a variety of tissues have similar characteristics," Kopan says. "The skin of these mice is easy to monitor and will give us the ability to further analyze tumor promotion and find answers that might apply to any chronic wound."

Funding from the National Institute of General Medical Sciences supported this research.


Story Source:

The above story is based on materials provided by Washington University School of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Demehri S, Turkoz A, Kopan R. Epidermal Notch1 loss promotes skin tumorigenesis by impacting the stromal microenvironment. Cancer Cell, July 7, 2009

Cite This Page:

Washington University School of Medicine. "Mice With Skin Condition Help Scientists Understand Tumor Growth." ScienceDaily. ScienceDaily, 9 July 2009. <www.sciencedaily.com/releases/2009/07/090706134052.htm>.
Washington University School of Medicine. (2009, July 9). Mice With Skin Condition Help Scientists Understand Tumor Growth. ScienceDaily. Retrieved October 30, 2014 from www.sciencedaily.com/releases/2009/07/090706134052.htm
Washington University School of Medicine. "Mice With Skin Condition Help Scientists Understand Tumor Growth." ScienceDaily. www.sciencedaily.com/releases/2009/07/090706134052.htm (accessed October 30, 2014).

Share This



More Health & Medicine News

Thursday, October 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Mind-Controlled Prosthetic Arm Restores Amputee Dexterity

Mind-Controlled Prosthetic Arm Restores Amputee Dexterity

Reuters - Innovations Video Online (Oct. 29, 2014) A Swedish amputee who became the first person to ever receive a brain controlled prosthetic arm is able to manipulate and handle delicate objects with an unprecedented level of dexterity. The device is connected directly to his bone, nerves and muscles, giving him the ability to control it with his thoughts. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Google To Use Nanoparticles, Wearables To Detect Disease

Google To Use Nanoparticles, Wearables To Detect Disease

Newsy (Oct. 29, 2014) Google X wants to improve modern medicine with nanoparticles and a wearable device. It's all an attempt to tackle disease detection and prevention. Video provided by Newsy
Powered by NewsLook.com
Can Drinking Milk Lead To Early Death?

Can Drinking Milk Lead To Early Death?

Newsy (Oct. 29, 2014) Researchers in Sweden released a study showing heavy milk drinkers face an increased mortality risk from a variety of causes. Video provided by Newsy
Powered by NewsLook.com
Obama: The US Will Not 'run and Hide' From Ebola

Obama: The US Will Not 'run and Hide' From Ebola

AP (Oct. 29, 2014) Surrounded by health care workers in the White House East Room, President Barack Obama said the U.S. will likely see additional Ebola cases in the weeks ahead. But he said the nation can't seal itself off in the fight against the disease. (Oct. 29) Video provided by AP
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