BACKGROUND/AIM: Melanoma is a skin cancer without effective therapy, showing high immunogenicity and mostly partial spontaneous regression (SR). The exact mechanisms of SR are still not well understood; therefore, the use of animal melanoma models is necessary to unravel the immunological processes during SR. MATERIALS AND METHODS: Skin melanoma samples (n=57) and peripheral blood samples (n=57) from the same animals were collected. Melanoma-bearing Libechov Minipigs (MeLiM) aged 3, 4, 6, 8, 10, 12, 20, and 32 weeks were used, and samples were analysed by flow cytometry for detection of immune cell subpopulations. RESULTS: The proportion of CD3-CD8+ (NK) cells in melanoma samples was found to be higher compared to blood samples at 6-8 weeks of age and then at 12 weeks of age. The population of CD4+CD8+ (effector/memory T helper) cells and CD4-CD8+ (cytotoxic T and NK) cells was also increased in melanoma compared to blood samples in 10-32-week-old pigs. The proportion of CD4-CD8+ cells in melanoma samples, then augmented until the 32nd week. On the contrary, the proportion of CD4+CD8- (naive T helper) cells was lower in melanoma samples versus blood samples in 6-32-week-old animals. CONCLUSION: Cytotoxic T cells were the most abundant population of tumour infiltrating immune cells found in MeLiM melanomas of animals aged 10-32 weeks, probably causing the destruction of melanoma cells. Furthermore, the development of specific (adaptive) immune response represented mainly by cytotoxic T cells seems to be crucial for the successful SR of porcine melanoma.
BACKGROUND/AIM: Melanoma is a cancer disease with increasing incidence in the Caucasian population. It is often accompanied by spontaneous regression (SR), probably due to high immunogenicity. Understanding of this phenomenon could allow its induction in clinical practice, but detailed study in humans is impossible for ethical reasons. The aim of this study was to determine the role of fibronectin, tenascin C, and MMP-2 in the process of SR. MATERIALS AND METHODS: Time-lapse study of SR was performed in the MeLiM (Melanoma-bearing Libechov Minipig) model. Skin melanomas were taken from 3 weeks to 8 months of age and immunohistochemically processed for fibronectin, tenascin C and matrix metalloproteinase-2 (MMP-2). RESULTS: Expression of all studied proteins increased up to the 10th week of age. Two structurally different areas were distinguishable from the 3rd month of age. MPP-2 expression predominated in areas with melanoma cells, whereas fibronectin and tenascin-C prevailed in the forming fibrous tissue. CONCLUSION: Rebuilding of melanoma into the fibrous tissue during SR was connected with a general rise in fibronectin and tenascin C expression.
Spontaneous regression (SR) of human melanoma is a rare, well-documented phenomenon that is not still fully understood. Its detailed study cannot be performed in patients due to ethical reasons. Using the Melanoma-bearing Libechov Minipig (MeLiM) animals of various ages (from 3 weeks to 8 months) we implemented a long-term monitoring of melanoma growth and SR. We focused on immunohistochemical detection of two important extracellular matrix proteins, collagen IV and laminin, which are associated with cancer. We showed that SR of melanoma is a highly dynamic process. The expression of collagen IV and laminin correlated with changes in population of melanoma cells. Tumours of 3-week-old animals consisted primarily of melanoma cells with a granular expression of collagen IV and laminin around them. Thereafter, melanoma cells were gradually destroyed and tumour tissue was rebuilt into the connective tissue. Collagen IV expression slightly increased in tumours of 10-week-old pigs showing extracellular fibrous appearance. In tumours of older animals, areas lacking melanoma cells demonstrated a low expression and areas still containing melanoma cells a high expression of both proteins. We considered the age of 10 weeks as a turning point in the transition between tumour growth and SR of the MeLiM melanoma.
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