A novel gene defect that causes a hereditary blistering disorder of the skin, epidermolysis bullosa, was identified in dogs.
Credit: Hannes Lohi research group

Researchers at the University of Helsinki have identified a novel gene defect that causes a hereditary blistering disorder of the skin, epidermolysis bullosa, in dogs. Epidermolysis bullosa, found in the Central Asian Shepherd dog breed, occurs also in humans due to an identical gene found in both canines and humans.

Furthermore, the dermatologists and biologists found new potential targets for the development of drugs. Dr. Venugopal Rao Mittapalli, Prof. Dr. Leena Bruckner-Tuderman, Dr. Dimitra Kiritsi and Dr. Alexander Nyström from the Medical Center — University of Freiburg conducted the study in cooperation with Juniorprofessor Dr. Winfried Römer and Dr. Josef Madl from the University of Freiburg and BIOSS Centre for Biological Signalling Studies. The team published the research findings in the journal “Cancer Research.”
Epidermolysis Bullosa, also known as butterfly disease, is a genetic skin condition. The skin of patients with this disease is as fragile as the wings of a butterfly. It blisters easily in response to minor injury or friction such as rubbing or scratching. Furthermore, the patients develop chronic wounds that are not healing and their fingers and toes fuse, for example. The condition is caused by a mutation of the gene COL7A1, which contains the blueprint for the protein collagen VII. This protein helps to bind the epidermis and the dermis, two layers of the skin, together. In RDEB patient, collagen VII is completely absent and, therefore, the skin becomes fragile.
So far, little was known about the molecular mechanisms connecting squamous cell carcinomas and RDEB. The Freiburg research team discovered that the cancer progresses rapidly in RDEB patients, because the repeated mechanical injury alters the dermis. The amount of proteins called pro-fibrotic growth factors increases, thereby increasing stiffness of the dermis. This environment helps the tumour cells to spread.
The researchers have also identified mechanisms that could be potential drug targets. For example, molecules that inhibit the growth factor TGF reduce the stiffness and the spread of the RDEB cancer cells. “The new knowledge we have gained facilitates the design of prophylactic and therapeutic measures for delaying tumour progression and extending cancer-free periods in RDEB,” says Venugopal Rao Mittapalli, the first author of the study.

Story Source: Materials provided byAlbert-Ludwigs-Universität Freiburg. Note: Content may be edited for style and length.

Journal Reference:
V. R. Mittapalli, J. Madl, S. Lo ffek, D. Kiritsi, J. S. Kern, W. Ro mer, A. Nystro m, L. Bruckner-Tuderman.Injury-Driven Stiffening of the Dermis Expedites Skin Carcinoma Progression. Cancer Research, 2015; 76 (4): 940 DOI: 10.1158/0008-5472.CAN-15-1348

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