Mice with skin help scientists tumor growth

Cancer sometimes to injuries and chronic wounds, but also why is not quite clear. Now, researchers at Washington University School of Medicine in St. Louis has changed from mouse to a decline, as the injury of the skin, and mice to help promote tumor effect of long wounds and injuries .

"The chronic condition of the skin of mice has led to development of skin cancers," says Raphael Kopan, Ph.D., professor of developmental biology and dermatology. "And what we have learned, this process corresponds very well with the new knowledge, a tumor that the environment plays a crucial role in development."

Summary of evidence in the clinical setting of chronic wounds of the skin, such as leg ulcers with an increased risk of skin cancer, and some scientists have suggested that chronic damage different organs may predispose to cancer.

In this study, published in the July 7 edition of Cancer Cell, researchers have discovered that chronic skin secretion of molecules, cells activated, skin, increases the number of blood vessels and local inflammation, increased the idea that the repair mechanisms of injury and inflammation are important in promoting cancer. The skin has been developed in mice by the inactivation of a gene called Notch1 in patches of skin cells, so that the rest of the skin intact. Notch1 is a master controller for normal skin and development has been designed to remove the tumor growth in cells of the skin, where it resides.

Without Notch1, patches of the skin of mice was small, denser and more pronounced. Given that mice with age, benign tumors, called the papillomas. More than 10 percent of these tumors spontaneously at an advanced stage, basal cell carcinoma, the most common form of skin cancer in humans.

It is important that further analysis has shown that Hautmalignomen had both mutant and normal cells of the skin. Since normal cells contain active Notch1, they did not expect that tumors, which was an important indication that other factors such as lack of Notch1 was responsible for tumor formation in the skin.

"The loss of Notch1 signaling in the transformation of skin cells to injury, both the mutants and the cells of normal skin to sensitive for cancer," Kopan said.

The research team showed that skin patches mutant promotes the growth of small blood vessels and the production of growth factors, expression, if the temporary help repair skin. The persistence of the expression of these factors, the cells in nutrients and indicates that the spread of the tumor to promote education, Kopan said. Many immune system cells secreting additional factors of abnormal skin patches and adjacent cells in inflammation.

Recently, drugs that decrease the activity of Notch1 have been used for Alzheimer's disease and to treat certain forms of cancer - Notch1 because, paradoxically, may be a tumor promoter in other tissues such as skin. Kopan said his study shows that the skin is very sensitive on the reduction of Notch1 activity. Long-term use of these drugs and others, the integrity of the skin, could be compromised with an increased risk of skin cancer, "he says.

"The study suggests that researchers are developing drugs, they should ensure that their potential impact on the skin, especially those that are chronic and cause damage to skin integrity," Kopan said. "Studies such as using our bandwidth complications in developing drugs and therapies to help prevent them. "

The researchers also plan the use of Notch-deficient mice, which provides a system in which molecules and identify the cellular interactions, the oncogenic effect of chronic wounds. Based on this analysis can be identified for new drug therapies for skin cancer and possibly other organs.

"It is reasonable to assume that chronic wounds, in a large number of tissues have properties," said Kopan. "The skin of the mouse is easy to observe and we will continue to analyze the tumor promotion and to find answers to all the chronic injury."