EMT definition
loss of epithelial cell polarity, junctions and adhesions to gain migratory and invasive properties and form mesenchymal cells
common in the formation and metastasis of carcinomas
3 types of EMT
- MESENCHYMAL:
- neural tube in the third week of gestation release cells forming neural crest that have epithelial origin but then migrate via EMT and become mesenchymal and responsible of CT
-gastrulation: formation of the mesoderm occurs via EMT of the uper germ layer cells - FIBROBLAST: wound healing, slightly more pathological: epithelial cells become fibroblasts accummulating collagen for fibrosis
- METASTATIC: carcinoma development and metastasis - destruction of basement membrane and movement intoblood vessels of underlying CT to migrate
characteristic epithelial markers
e-cadherins
cytokeratins
occludins and ZO1
desmoplakins
lamin
characteristics mesenchymal markers
n-cadherins
vimentin
fibronectin
alpa SMA
collagen type 1
MMPs
change in actin cytoskeleton over the EMT process
cortical actin in epithelial cells is lost and reverted into bundles of actin filaments in fibroblasts that optimise motility
what triggers the EMT process
upregulation of certain transcription factors like snail and twist
what is the result of MMP upregualation in the mesenchymal cells produced
matrix metalloproteinases
destroy components of ECM
allows increased cell motility
2 types of carcinomas examples
- renal cell: loss of e-cadherin and B-catenin, express vimentin but actin is still present –> no defined phenotype
- pancreatic cell: very agressive, e-cadherin/B-catenins are still expressed, negative for vimentin BUT express proteins that destroy basemement membrane
!! this occurs because cells do not become completely mesenchymal or epithelial –> EMT is NOT a not-or-all process so there are intermediate phenotypes
process of analysis of the carcinomas formed
2D monolayer or 3D spheroid models: analysis of the diff factors expressed and the degree of their expression
