Core C - Meenhard HerlynThis Cell Biology Core has major resources available that are provided to the program project investigators,including melanocytes, keratinocytes, fibroblasts, endothelial cells, bone marrow-derived mesenchymal stemcells, melanoma cells, monoclonal antibodies to melanoma-associated antigens, adenoviral and lentiviralvectors for growth factors, adhesion molecules, and oncogenes.Three-dimensional cultures of normal human skin (skin equivalents, organotypic cultures of skin) with a'dermis' of fibroblasts embedded in collagen and an 'epidermis' of melanocytes/melanoma cells andkeratinocytes are generated and provided to the program investigators. This three-dimensional model issuperior to two- dimensional culture because it mimics the in vivo context for the melanocytes/melanomacells. For screening studies, the Core is providing a spheroid culture model that allows investigations onmelanoma cells intimately interacting with stromal cells.The Core provides to program members orthotopic in vivo models of melanoma growth. Due to the differentarchitectures between mouse and human skin, melanomas, including xenografted cells, cannot be grown inthe natural murine skin environment. Instead, the Core will first graft human skin onto immunodeficient mice.When the skin has healed, we will inject human melanoma cells intradermally, where growth and invasionoccurs in the same way as in patients' lesions. The Core is also providing the subcutaneous melanomagrowth model for standard experiments. Besides providing resources to the other projects, the Core will testcompounds developed in Projects 3 and 4 and initially selected in Project 1. The responsibility of the Core isin testing expanded number of cell lines, in quality control testing of compounds through the differentbiological assays and through Western blotting. The Core also trains investigators of the Program in alltumor biological assays. Overall, this Core will provide efficient and high quality service to all interestedlaboratories within this Program Project.
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