Melanoma Lecture 3.doc

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Western University
Anatomy and Cell Biology
Anatomy and Cell Biology 4461B
Geordie Shepherd

LP Lecture 3: Melanoma Translational Models of Melanoma Organotypic Cultures • Construct human skin in vitro • Used for burns and other studies • Consist of terminally differentiated epidermal and epidermal and dermal cell types • Can add or induce melanomas and watch progression • Can graft into mice to study metastasis Xenografts • Human tumor cells grown in immunocompromised mice intra-dermally • Only VGP and metastatic melanoma cells • New models use other species such as zebrafish which allow for imaging and screening Mouse Models • Classic chemical induction • DMBA rubbed on skin • Carcinogens induce tumor formation • Allografts • Transplantable murine melanoma cell lines • Transgenic Mouse Models • Relatively specific due to proteins that are unique to melanocytes in pigment produc- tion such as tyrosinase and metallothionein • Many known mutations in melanoma • Tyrosinase promoter driven SV-40 oncogenic protein • C-Ret oncogene driven by inducible metallothionein promoter • Hepatocyte growth factor expression driven by metallotheionein promoter H-ras driven by tyrosinase promoter in INK4A knockout mice • • Zebrafish BRAF mutation causes moles • • Crossed with p53 mutation, it forms melanomas Translational Pipeline Example • Knew that metastatic melanoma cells are poorly differentiated (stem cell like) and that this allowed them to metastasize • Compared metastatic and RGP lesion cells • Metastatic cells • No pigment • Highly invasive • Undergoes anchorage independent growth • Readily
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