Session 8: Neoplasia 2 Flashcards
What are the most lethal features of a malignant neoplasm?
The ability to invade and spread to distant sites. This leads to a greatly increased tumour burden.
What are the required steps for a malignant cell to get from a primary site to a secondary site.
1: Grow + invade primary site
2: Enter a transport system and lodge at a secondary site
3: Grow at the secondary site to form a new tumour.
At all points the cells must evade destruction by immune cells.
Invasion involves three important alterations.
Which?
Altered adhesion
Stromal proteolysis
Motility
Explain epithelial to mesenchymal transition (EMT).
The three alterations create a carcinoma cell phenotype that sometimes appears more like mesenchymal cell than an epithelial cell.
Explain altered adhesion.
This is between malignant cells and involves reduciton in E-cadherin expression (which binds malignant cells to malignant cells)
The altered adhesion between malignant cells and stromal proteins involves changes in integrin expression as well (an upregulation) where the malignant cells bind more tightly to the stroma.
Explain stromal proteolysis.
Once attached and tightly bound to the stroma the malignant cell needs to enter the tissue and does so by degrading the basement membrane and also the stroma. This is by an altered expression of proteases, most notably matrix metalloproteinases (MMPs). Malignant cells take advatage of nearby non-neoplastic cells which together form a cancer niche. These normal cells provide some growth factors and proteases for the malignant cells.
Explain altered motility.
Involves changes in the actin cytoskeleton.
Signalling through integrins is important and occurs via small G proteins such as members of Rho family.
What are the three routes for which malignant cells can travel to distant sites?
Entering blood vessels via capillaries and venules
Entering lymphatic vessels
Entering fluid in body cavities like pleura, peritoneal, pericardial, and brain ventricles. This is known as transcoelomic spread.
How can malignant cells enter blood vessels?
As a tumour grows the inner most cells will eventually get hypoxic. In order to counteract this neovascularisation is needed so new blood vessels are formed within the tumour itself.
What is colonisation?
The growth of malignant cells at a secondary site.
What part of metastasis is the greatest barrier?
Failed colonisation.
What happens in failed colonisation?
Most malignant cells lodge at secondary sites as tiny clinically undetectable cell clusters that either die or fail to grow into detectable tumours.
The ones that fail to grow into detectable tumours are called micrometastases.
What is the risk of micrometastases?
They are undetectable. This means that a patient can be declared free of their cancer and still harbour micrometastases.
This is called tumour dormancy.
This also means that a malignant neoplasm relapse can occur years later after being ‘cured’.
What determines the site of a secondary tumour?
Site of a secondary neoplasm depends on:
Regional drainage of blood, lymph or coelomic fluid.
‘Seed and soil’ phenomenon which may explain the seemingly unpredictable distribution of blood-borne metastases due to interactions between malignant cells and the local tumour environment.
Where does lymphatic metastasis usually end up?
To draining lymph nodes.
