9. Neoplasms Flashcards
What increases tumour burden?
The ability of malignant cells to invade and spread to distant sites.
How many cancer cells will be in 1kg of tumour?
1 trillion cells.
What three steps are all required for malignant cells to get from a primary site to a secondary site?
1) grow and invade at the primary site.
2) enter a transport system and lodge at a secondary site.
3) grow at the secondary site to form a new tumour (colonisation).
What makes the process of invasion and metastasis of tumours inefficient?
All three steps - grow at primary site, enter transport system, and grow a secondary site, have to be successful whilst evading destruction by immune cells. The vast majority fail in transport or growing in the new secondary site conditions.
What three alterations must carcinoma cells undergo to invade surrounding tissues?
Altered adhesion, altered stromal proteolysis and altered motility.
What is epitehlial-to-mesenchymal transition?
When carcinoma cells undergo alterations to adhesion, stromal proteolysis, and motility so they become more like mesenchymal cells than epithelial cells.
What does altered adhesion between malignant cells involve?
A reduction in E-cadherin expression.
What does altered adhesion between malignant cells ad stromal proteins involve?
Changes in integrin expression. The cells must degrade the basement membrane of the stroma to invade.
Why is matrix metalloproteinases important for invasion of carcinoma cells?
It’s expression must be altered to degrade the basement membrane or the stroma. It helps malignant cells take advantage of nearby non-neoplastic cells, to form a cancer niche.
How is motility of carcinoma cells altered?
By changes to the actin cytoskeleton.
What are members of the Rho family used for in motility changes?
Signalling through integrins occurs via small G proteins like members of the Rho family.
What are the three options for transport for malignant cells?
Entering: the blood vessels via capillaries and venules, or the lymphatic vessels, or fluid in the body cavities (pleura, peritoneal, pericardial and brain ventricles) in transcoelomic spread.
How can lymphangiogenesis be a useful indicator of?
Survival rate and metastasis of a tumour.
What is a colonisation?
A secondary site where malignant cells grow.
What is the greatest barrier to successful formation of metastasis?
Failed colonisation.
What are micrometastases?
Surviving microscopic deposits that fail to grow.
What is tumour dormancy?
Where a clinically ‘disease-free’ person harbours many micrometastases.
What causes a malignant neoplasm to relapse, years after an apparent cure?
Typically one or two micrometastases start to grow.
What causes dormancy?
The hostility of the secondary site the malignant tumour is trying to grow in. The metastases need to relearn how to undergo angiogenesis in the new site.
What two factor determine where a metastases goes?
The regional drainage of the blood, lymph, or coelomic fluid, and the seed and soil phenomenon.
Where will metastases move to in transcoelomic spread?
Predictably to other areas in the coelomic space or to adjacent organs.
Where will metastases grow in blood-borne spread?
Sometimes, but not always, in the next capillary bed that the cells encounter.
What can the seed and soil phenomenon explain?
The seemingly unpredictable distribution of blood-borne metastases.
What is the seed and soil phenomenon?
The seed is the cancer cell and the soil is the organ or niche of the secondary site. The soil has to be right for the seed to grow, there needs to be successful interactions between malignant cells and the local tumour environment.
