Role of tumor microenvironment in the formation and progression of skin melanoma
Journal Title: Advances in Hygiene and Experimental Medicine - Year 2013, Vol 67, Issue 0
Abstract
Melanoma develops from melanocytes localized mainly in skin, to a lesser extent in uvea and mucosal tissue. It is one of the most aggressive tumors, resistant to standard therapies. It is caused mainly by UV radiation. Approximately 10% of melanomas have a familial background. Transformation of melanocytes is driven mainly by mutations in genes coding for proteins regulating proliferation, cell growth, cell cycle, and death. Although genetic changes are indisputable causes of melanoma formation, the key role of the skin microenvironment is becoming more and more acknowledged. Normal cells of the skin, such as keratinocytes, fibroblasts, endothelial, and immune cells, alongside melanocytes constitute a special microenvironment in which disturbed homeostasis may facilitate melanoma development. The process of transformation is initiated by aberrant interaction of keratinocytes and melanocytes. Proliferation and invasive growth of the developing neoplasm may be further facilitated by myofibroblasts as well as macrophages residing within the tumor. They are able to stimulate angiogenesis and suppress the immune response. Macrophages may, additionally, create aggressive hybrid cells through fusion with melanoma cells. Indispensable in the process of metastasis are endothelial cells which co-form blood vessels, the main routes of tumor cells’ seeding. All of the aforementioned processes take place in a tumor growth-promoting atmosphere of low oxygen tension in the skin, further decreasing during tumor growth. Probably the tumor growth-promoting microenvironment is one of the main factors responsible for melanoma aggressiveness.
Authors and Affiliations
Magdalena Olbryt
Keywords
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