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MatTek Technical Reference TR-365:
RECONSTRUCTED HUMAN SKIN MODEL TO STUDY MELANOMA AT DIFFERENT STAGES OF PROGRESSION. Kaluzhny, Y., Sur, G., Klausner, M. MatTek Corporation, Ashland, MA, United States. Presented at Society of Investigative Dermatology, St.Louis, MO, May 4-7, (2005).
Summary:
The incidence of cutaneous melanoma (CM) has increased dramatically in the last few decades. The changes leading from treatable radial growth phase (RGP) melanoma, to high risk vertical growth phase (VGP), and finally to the metastatic melanoma (MM) phenotype are not well understood. Development of specific RGP, VGP, and MM tissue models along with their specific microenvironments and cell-matrix and cell-to-cell communication are crucial for understanding disease progression and for the development of CM therapies. A serum-free (SF) culture system, in which the precise effects of growth factors and chemo-therapeutic compounds can be tested without interference from the multitude of undetermined components in serum, is presented. The culture system is based on the previously-developed, highly differentiated full thickness skin model system, EpiDerm™ Full Thickness (EpiDermFT™), which exhibits a fully developed basement membrane zone. Single cell suspensions of normal human epidermal keratinocytes and melanoma cells from different stages of melanoma progression are seeded on fibroblast-contracted collagen gels and induced to differentiate in SF medium. Incorporation of RGP cells leads to the development of small melanoma nodes in the epidermis which can be detected histologically at day 10 of culture. By day 39, the melanoma cells take over the epidermis but melanoma nodes do not spread into the dermis. Incorporation of the MM cell lines, A375 and SK-MEL-28, results in progressively growing clusters of melanoma cells at the dermal/epidermal junction. These clusters begin to invade the dermis by day 14. Expression of the adhesion molecule, N-cadherin, by melanoma cells in the reconstructed skin model parallels in vivo expression in stage-specific melanoma. The development of three dimensional, serum-free tissue culture models, containing melanocytes at different stages of CM malignancy, will provide researchers with valuable tools to study, understand, and develop preventative and therapeutic treatments for this serious cutaneous malignancy.
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