05 December 2017

Caught red-handed

A group of scientists from the German Cancer Research Center (DKFZ) has demonstrated in vivo that the human papillomavirus (HPV) in combination with UV radiation provokes non-melanoma skin cancer.

Almost every person is infected with the "skin type" of HPV. As a rule, infection occurs in childhood. A healthy body is able to suppress the virus, but closer to old age, the immune system weakens. Also at risk are patients who have undergone organ transplantation and are forced to take immune suppressing drugs for life to prevent transplant rejection. The risk of developing non-melanoma skin cancer in this group of people is up to 250 times higher compared to healthy people.

The main reason for the development of non–melanoma skin cancer is intense exposure to UV radiation. To prove that HPV also increases the risk of non-melanoma cancer, the researchers compared mice infected with HPV immediately after birth with mice raised in a completely virus-free environment. They exposed both groups of mice to UV radiation at a dose comparable to that received by the average tourist on the Mediterranean coast. Non-melanoma skin cancer developed only in a group of mice infected with HPV. Not a single mouse from the control group got sick.

The researchers noticed that some mice with HPV under the influence of UV radiation developed cancer with elements of keratinization (squamous cell carcinoma), while the rest of the mice had no keratinization processes.

 carcinoma.jpgSquamous cell carcinoma (red: E-cadherin, green: vimentin, blue: cell nuclei).
Source: article by D.Hasche et al.

The tissue sample of squamous cell keratinizing cancer contained a large number of viruses, as in a precancerous condition called "actinic keratosis". This type of cancer is characterized by excessive growth of atypical cells resembling human skin in structure, and refers to highly differentiated tumors. Researchers have found that HPV is able to disrupt the stability of the DNA of the host cell and leads to the accumulation of defects produced by UV radiation.

Another group of tumors did not contain viruses, although antibodies to HPV were found in the blood of animals, which indicates that the body was infected with the virus. In this group of tumors, there was a high number of mutations in the p53 gene, which is vital for cells and is considered the "keeper of the genome". In humans, the p53 gene is also faulty in squamous cell carcinoma, which leads to uncontrolled cell growth.

The conducted experiment was able to prove the important role of HPV in the development of non-melanoma skin cancer in a living organism.

The faster cell division occurs and the lower the degree of differentiation, the more aggressive the cancer. According to the study, by provoking the appearance of a tumor, viruses subsequently inhibited the division and growth of tumor cells. In other words, the amount of virus in the tumor tissue is related to the degree of its differentiation.

The authors plan to further study HPV as a cause of non-melanoma skin cancer. The results of this work will help to develop HPV vaccines, which is especially important for the elderly, as well as patients in a state of drug immunodeficiency after organ transplantation.

Article by Daniel Hasche et al. The interplay of UV and cutaneous papillomavirus infection in skin cancer development is published in the journal PLOS Pathogens.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of DKFZ: Caught in the act: Papillomaviruses promote non-melanoma skin cancer.

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