Anatomy and Cell Biology 4461B Lecture Notes - Lecture 3: Gene Therapy, Oncolytic Herpes Virus, Histocompatibility

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Published on 13 Jun 2012
School
Western University
Department
Anatomy and Cell Biology
Course
Anatomy and Cell Biology 4461B
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
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