Neoplasia 2 Flashcards
What are the most lethal features of malignant neoplasms?
Invasion and metastasis are the most lethal features of a malignant meoplasm.
The ability of malignant cells to invade and spread to distant sites leads to a greatly increased tumour burden. Untreated, this results in a vast number of “parasitic” malignant cells.
What must hapen for malignant cells to get from a primary to a secondary site?
- Grow and invade at the primary site
- Enter a transport system and lodge at a secondary site
- Grow at the secondary site to form a new tumour (colonisation).
At all these points, the cells must evade destruction by immune cells.
The whole process is inefficient.
What are the most inefficient steps of metastasis?
Travelling into capillaries - can get distroyed
Mostly, growing at different sites. (so will lodge but not grow)
What three important alterations occur during invasion?
- Altered Adhesion
- Proteolysis
- Motility
These three changes create a carcinoma cell phenotype that sometimes appears more like a mesenchymal cell than an epithelial cell, hence this is called epithelial-to-mesenchymal (stem cell) transition (EMT)
What occurs during adhesion?
Atered adhesion between malignant cells involves a reduction in E-cadherin expression. Altered adhesion between malignant cells and stromal proteins involves changes in integrin expression.
What occcrus during proteolysis?
The cells must degrade masement membrane and stroma to invade.
This involves the altered expression of proteases, notably matrix metalloproteinases (MMPs).
Malignant cells take advantage of the nearby non-neoplastic cells, which together form a cancer niche.
These normal cells provide some growth factors and proteases.
What occurs during motility?
Altered motility involves changes in the actin cytoskeletom. Signalling through integrins is important and accurs via small G proteins such as members of Rho family.
How do malignant cells get transported to distant sites?
- Blood vessles via capillaries and venules
- Lymphatic venules
- Fluid in body cavities (pleura, peritoneal, pericardial and brain ventricles) which is knwon as transcoelomic spread
How do malignant cells grow at secondary sites?
This is known as colonisation.
Failed colonisation is considered to be the greatetst barrier to successful formation of metastasis because many malignant cells lodge at secondary sites but these tiny cell clusters either die or fail to grow into clinically detectible tumours. Surviving microscopic deposits that fails to grow are called micrometastases.
Why can cancer patients not be organ donors?
Because an apparently disease-free person may harbour many micrometastases, a phenomenon known as tumour dormancy.
When a malignant neoplasm relapses years after apparent cure it is typically due to one or more micrometastases starting to grow.
What determines the site of a secondary tumour?
The site of a secondary neoplasm depends on:
- Regional drainage of blood, lymph or coelomic fluid.
- For lymphatic metastasis this is very predictable to draining lymph nodes.
- For transcoelomic spread this is predictably to other areas in the coelimic space or to adjacent organs.
- For blood-borne metastasis this is sometimes (but not always) to the next capillary bed that the cells encounter.
What is the soil and seen phenomenon?
This may explain the seemingly unpredictable dsitribution beween blood-borne metastases, is due to interactions between malignant cells and the local tumour environment (i.e. the niche) at the secondary site.
What is the difference between the spread of carcinomas and sarcomas?
- Carcinomas typically spread via lymphatics first whereas sarcomas tend to spread via the blood stream.
- Carcinomas typically spread to the first draining lymph node then to bloos borne distant sites.
- Common sites of blood borne metastasis are lung, bone, liver and brain.
What neoplasms most commonly spread to the brain?
The neoplasms that most frequently spread to the bone are breast, bronchus, kidney, thyroid and prostate.
What does it mean to say tumours have “personalities”?
This means that some neoplasms are more agressive and metastasise very early in their course, e.g. small cell bronchial carcinoma.
Others almost never mettastasise, e.g. basal cell carcinoma of the skin.
The likelyhood of the metastasis is related to the size of the primary neoplasm. This is the basis of cancer staging.
