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2013|14 Annual Report Fraunhofer IGB

8 4 IN-VITRO MODEL FOR HUMAN SQUAMOUS CELL CARCINOMA Dipl.-Biol. (t.o.) Sibylle Thude White skin cancer caused by UV radiation With 400,000 – ​600,000 new cases per year worldwide, hu- man squamous cell carcinoma (SCC) in addition to basal cell carcinoma are the most common types of skin cancer [1]. SCC has its origin in the development of atypical epidermal keratinocytes and may result from so-called precancerous tis- sue changes associated with an increased risk of cancer, such as actinic keratosis or Bowen’s disease [1]. Caused by chronic photo damage, white skin cancer occurs mainly in fair-skinned people with light-sensitive skin after years of exposure to UV. It primarily affects the skin areas on the head, forehead, nose, lips, forearms or hands, the human body’s most frequently ex- posed “sun terraces“. Despite high cure rates, the early treat- ment of superficial skin cancer is recommended because the formation of cancer metastases is still a potential threat [2]. New therapies require new test models In addition to the surgical removal of cancerous cells, other methods such as freezing (cryotherapy), X-ray surface irradia- tion, local chemotherapy and local immunotherapy are avail- able. A promising new therapeutic approach is photodynamic therapy (PDT), in which a chemical compound accumulates selectively in the tumor cells and makes them more sensitive to light. Subsequently, the tumor and the healthy tissue sur- rounding it are irradiated with light of a suitable wavelength. This photochemical process generates toxic substances, lead- ing to cell death. A minor side effect of this therapy is only a temporary light sensitivity of the irradiated skin. However, only a few photosensitizing agents are known and the effect of the radiation on normal cells have not been sufficiently studied. In the development of new drugs, new test methods that generate human relevant and translatable results are essential. New therapies are typically tested in animal trials and later on patients in clinical trials. Animal studies do not always reflect how a drug will work in the human body and clinical trials are very risky, causing great physical and psychological stress for the patient. However, the use of a three-dimensional skin cancer model could fill this gap in the development of new topical treatments. In vitro model depicts early and late tumor stage At the Fraunhofer IGB, we are developing a white skin cancer model for the testing of new photosensitizers that allow for the optimization of novel therapy approaches. We introduced white skin cancer cells (cell line SCC-25) into our well-estab- lished three-dimensional skin model creating the first in vitro model for squamous cell carcinoma. Various strategies have been used to integrate the SCC cell line into the skin model. When the SCC cells are simultane- ously introduced with healthy keratinocytes in defined ratios, both cell types can be co-cultured in the skin model produc- ing a test system that is morphologically comparable to the early stage of squamous cell carcinoma in humans. For late stages of the disease, full-thickness skin models were devel- oped where the epidermis is composed solely of SCC cells. In addition, SCC cells were integrated into the dermal part of the model to allow the development of tumor nests, which is similar to nests found in the very late stage of squamous cell carcinoma. Using Raman spectroscopy, we were able to non- destructively distinguish healthy keratinocytes from tumor cells in non-fixed model without the use of cell-specific markers. PHARMACY skin-in-a-dish model early disease-in-a-dish model late disease-in-a-dish modell keratinocytes fibroblasts SCC-25 cells 1

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