Flashcards in MOD 9 Deck (47)
What are the most lethal features of a malignant neoplasm and why?
The ability of malignant cells to invade and spread to distant sites leads to a greatly increased tumour burden. Untreated, this results in vast numbers of "parasitic" metastasis.
Define tumour burden:
The total mass of tumour tissue carried by an individual with malignancy.
Describe the multi-step journey malignant cells take to get from their primary to secondary sites:
1. Grow and invade at primary site
2. Enter a transport system and lodge at a secondary site
3. Grow at a the secondary site to form a new tumour (colonisation).
What do malignant cells need to evade throughout all steps in their invasion and metastatic journey?
Destruction by immune cells.
Why is invasion and metastasis by malignant cells inefficient?
Malignant cells often fail at:
1. Entering a vessel and lodging at a secondary site
2. Colonisation at the secondary site
How do benign tumours metastasise?
Which three important alterations does invasion require?
1. Altered adhesion
2. Stromal and basement membrane proteolysis
What is the epitheilial-to-mesenchymal transition (EMT)?
The changes to the carcinomal cell phenotype (altered adhesion, stromal proteolysis and motility) that occur which make the epithelial cell appear more like a mesenchymal cell.
How is altered adhesion between malignant cells acheived?
Reduced expression of E-cadherin.
How is altered adhesion between malignant cells and stromal proteins achieved?
Changes in Integrin expression.
How is stromal proteolysis achieved?
Altered expression of proteases, notably: matrix metalloproteinases.
What is the cancer niche?
The microenvironment that neoplastic cells are in. They can take advantage of neighbouring non-neoplastic cells which provide some growth factors and proteases.
How is altered motility achieved?
Changes in the actin cytoskeleton. Important in this process is signalling through Integrins which use small G proteins such as members of the Rho family.
What are the three routes that malignant cells can use to transport themselves to distant sites?
They can enter:
1. Blood vessels via capillaries and venules
2. Lymphatic vessels
3. Fluid in body cavities (pleura, peritoneal, pericardial and brain ventricle) = transcoelomic spread.
How can malignant cell transport by blood vessels be facilitated by the malignant cells?
They can stimulate angiogenesis creating new larger blood vessel which can transport the cancer cells. These are new and leaky, facilitating spread.
What is the greatest barrier to successful formation of metastasis?
Failed colonisation. Many malignant cells lodge at distal sites but these tiny clusters die or fail to grow into clinically detectable tumours (micrometastases).
What are micrometastases?
These are surviving microscopic deposits of malignant cells that fail to grow.
What is tumour dormany?
A stage in cancer progression where the cells cease dividing but survive in a quiescent state as micrometastases (producing no symptoms) while waiting for appropriate environmental conditions to begin proliferation again. This is why malignant neoplasm can relapse years after an apparent cure - typically one or more micrometastases starting to grow.
What determines the site of a secondary tumour?
1. Regional drainage of blood, lymph or coelomic fluid.
2. "seed and soil" phenomenon - microenviornment (niche) at secondary site.
When malignant cell are transported by lymph vessels where do they tend to spread?
Predictably to draining lymph nodes.
When malignant cell are transported by transcoelomic spread where do they tend to spread?
Other areas in the coelomic space or to adjacent organs.
When malignant cell are transported by blood vessels where do they tend to spread?
Sometime (but not always) to the next capillary bed that cells encounter.
What is the "seed and soil" phenomenon?
The interactions of some microenvironments (niche) at secondary sites with malignant cells may determine where blood-borne malignant cells spread to. This could explain the seemingly unpredictable distribution of blood-borne metastases.
Where do carcinomas tend to spread to first?
Typically spread via lymphatics first to lymph nodes and then to blood-borne distant sites.
Where do sarcomas tend to spread to first?
Tend to spread through bloodstream.
What are common sites of blood-borne metastases?
Lung, bone, liver and brain.
Which neoplasms most frequently spread to bone?
Breast, bronchus, kidney, thyroid and prostate.
What is meant by malignant tumours having "personalities"?
Some malignant neoplasms are more aggressive and metastasise very early in their course (e.g. small cell bronchiomal carcinoma). Others almost never metastasise (basal cell carcinoma of the skin).
How is the likelihood of metastasis (e.g. staging of a cancer) determined?
It is related to the size of the primary neoplasm.