Cancer invasion and metastasis Flashcards
(27 cards)
What % of cancer-related deaths are due to the primary tumour?
10%
What are the steps of the invasion-metastasis cascade?
Primary tumour formation localized invasion intravasation transport through circulation arrest in microvessels of various organs extravasation formation of micrometastases colonization- formation of macrometastases
What is the basement membrane?
Specialised extracellular matrix which is essential for the structure of a organ, also important for separating organs from the surrounding stroma
What is it called if a carcinoma is contained to the basement membrane?
The cancer is said to be benign if it is localised and contained
What is intravasation?
The process of cancerous cells entering the blood and lymphatic vessels
What interactions are thought to be essential for intravasation?
Interactions between the cancerous cells and macrophages and endothelial cells which make up vessel walls
interaction allows cancerous cells to enter the blood through the endothelial walls
What is extravasation?
The process of cancerous cells escaping the vessels and entering tissue
What is thought to facilitate extravasation?
Interaction between cancerous cells and macrophages
What happens when cancerous cells first arrive in new tissue?
They are situated in the parenchyma of the tissue and form small clumps of cancer cells= micrometastasis
Why is colonisation so difficult?
The cancerous cells are in a different environment to their native environment- dont receive the same signals etc
What is metastatic inefficiency?
The general inefficiency of the invasion/metastasis process
few individual cells complete the whole process- many wont survive
Why do cancer cells undergo an epithelial-to-mesenchymal transition?
Epithelial cells are firmly attached to one another and the basement membrane- they arent mobile cells
to be able to migrate these cells must change their phenotype
What is lost in the EMT?
Cytokeratin expression
tight junction and adherence junctions involving E-cadherin
epithelial cell polarity
epithelial gene expression- e.g catenins
What is gained in the EMT?
A fibroblast like shape motility and invasiveness mesenchymal gene expression e.g fibronectin protease secretion vimentin expression
What is single cell migration?
The migration of cells independent of cell-cell interactions
cells migration is not dependent on its neighbours migration pattern
What are the types of single cell migration?
Amoeboid like- round cell body with blebbing protrusions
Mesenchymal-like- elongated cell body with longer protrusions
What are the types of collective cell migration?
Narrow linear strands- lead by one leader
Irregularly shaped sheets- multiple cells in diameter- lead by several leader cells
What is migration plasticity?
When cancer cells can switch between different migration modes- individual to collective and vice versa
Why is migration plasticity a problem when trying to block metastasis?
Blocking a single migration mode isn’t helpful when cancer cells can just switch to another
Whats a new strategy for trying to block metastasis?
Targeting the master regulators which controls a cell’s ability to switch - hinder the cells ability to switch
P53 affects what- as well as cell cycle control and apoptosis-?
Cell migration and invasiveness
How does P53 oppose EMT?
P53 inhibits the loss of cell-cell junctions
BUT not the mutant form of P53
What does mutant P53 promote?- what cancer is it associated with
An aggressive cancer phenotype -
mutant P53 is found in 50-75% of pancreatic ductal adenocarcinomas
What model showed the difference between null P53 and mutant p53?
Transgenic mice model
cre-recombinase
1st mouse-stop codon upstream of a pancreas specific promoter and P53 floxed, (k-ras also under control of this promoter)
cre recognises the lox-p sites and removes whats in between
activation of ras and removal of p53
2nd mouse- p53 is not floxed
expression of ras and mutant p53
