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Flashcards in The hallmarks of cancer Deck (25):

What are the stages of the metastasis cascade

primary tumour
Localised invasion of surrounding tissue
Intravasation - invasion of cancer cells through the basal membrane into a blood vessel
Transport through circulation
Arrest in microvessels of various organs
Extravasation of surrounding tissues and form micrometastases followed by large ones.


What is the basement membrane

A specialised extracellular matrix that surrounds the epithelia.


When are carcinomas considered benign?

If they are contained within the basement membrane


Do cancer cells acquire the ability to breach the basement membrane and invade nearby stroma singly or in groups?



How does intravasation occur

Studies suggest that the interation with macrophages and endothelial cells enables breast cancer cells to invade through the endothelial wall.


What kind of an environment is the blood for cancer

Actively hostile - only a tiny proportion of circulating tumour cells are successful in founding new metastatic colonies.


Does the location of the primary tumour have any influence on the area of metastasis

Yes - preferentially moves to specific organs depending on primary location - unsure why


What are the three main sites of metastasis

Lungs, Bone, Brain


What do the cancer cells do once they are trapped in one of the organs

Escape by extravasation
The opposite of intravasation
Again suggested to be by an interaction between cancer cells and macrophages


What is colonisation

The growth of microscopic metasteses and is the most difficult step for a cancer as the foreign environment does not provide the support that the cancer cells had in their primary site.


How does localised invasion occur?

Epithelial to mesenchymal transition (EMT)


What is required for EMT to occur

Lose following features:
Expression of cytokeratin, E-cadherin, Epithelial polarity and epithelial gene expression
Fibroblast like shape, Mobility and invasiveness, Mesenchymal gene expression (Fibronectin), Protease secretion to degrade the surrounding basement membrane


How do cancer cells move after leaving the primary tumour?

Display many modes of migration (able to adapt to different environmental conditions, assuming different morphologies and migration characteristics in order to stay mobile)


What is single cell migration

Lack of cell-cell interation
Low correlation of the cell and its neighbours
Cells can display different phenotypes


What are the different phenotypes of single migrating cells

1: Amoeboid like has a round cell body with short or blebbing protrusion
2: Mesenchymal like cell are elongated cell bodies and longer protrusions


What is collective cell migration

Groups of cells retain cell-cell adhesions. They move as either a narrow linear strand or as broad irregular sheets.


What is required of the leader cells of collective migrating cells

Mesenchymal characteristics - able to degrade the ECM around them


What is migration plasticity

Cancer cells have the ability to switch between migration modes - which makes it challenging to design anti-metastatic pathways that target a single migratory mode.


How do Anti-metastatic therapies target migrator modes

Target the master regulators that control and allow the cancerous cells to switch between the different modes of migration.


Is mutant p53 expression the same as null p53

Not completely - mutant p53 can also acquire new functions to drive cell migration, invasion and metastasis


What is the role of p53 in regard to EMT and cell migration

p53 prevents the loss of cell-cell junctions, opposing EMT.
It inhibits the activity of a variety of pro-migratory proteins, resulting in the reduction of cell migration and invasion.


How does mutant p53 promote an aggressive cancer phenotype (pancreatic cancer as 50-75% of PDAC have p53 mutations, following the mutation of kras)

Results in the expression of a stable mutant (R175H) rather than the loss of p53 expression.


What were the two mouse models for PDAC

LoxP mouse with a specific promoter found in the pancreas.
Stop codon for mutant k-ras is floxed as is p53. So when Cre recombinase is expressed: k-ras is expressed and the p53 is lost (in the pancreas)
2nd mouse
Same as previous but now a stop codon is floxed infront of the mutated p53.
This allows for the comparison of mice with no p53 or with mutant p53


What was the result of p53 mutant expression vs no expression in the PDAC mouse

mutant p53: half the mice had metastases whereas the p53 null mice had no metastases.


How does mutant p53 encourage metastases

It promotes the recycling of integrins and growth factor receptors from the endosome to the plasma membrane.
The increased recycling sustains downstream akt signalling, promoting cancer cell invasion and metastasis