Tumour Biology Flashcards
Define metastasis.
A tumour deposit that is discontinuous with the primary tumour.
List the processes involved in the metastatic cascade.
1 - Detachment from primary tumour and invasion of extracellular matrix.
2 - Intravasation.
3 - Migration.
4 - Extravasation.
5 - Colonisation.
*The rest of the lecture goes through each of these points in order.
What is the rate limiting step in metastasis?
Why might this be?
- Colonisation.
- This is because most metastatic cells die after extravasating because they are unlikely to be adapted to the new environment.
What facilitates detachment of metastatic cells from the primary tumour?
Downregulation of adhesion molecules such as E-cadherin.
In which cells are E-cadherins most common?
Epithelial cells.
How does E-cadherin work?
- Two E-cadherin molecules on cell surfaces bind to a cell’s actin filament by binding to beta catenin on the actin filaments.
- E-cadherin molecules on other cell surfaces bind to other E-cadherin molecules, linking the actin filaments.
What happens to beta catenin if E-cadherin is not present to bind to it?
Why is this important?
- It becomes free in the cytoplasm, triggering a failsafe response which clears beta catenin from the cell by way of the ubiquitin-proteasome system.
- This is important because free beta catenin is carcinogenic.
What is APC?
A tumour suppressor gene which acts as a negative regulator of beta catenin.
List 2 biological processes that are particularly common in the formation of colorectal cancer.
What is the common effect of these biological processes?
1 - E-cadherin is downregulated.
2 - APC is deleted, leading to the loss of its expression.
- These processes cause an increase in free beta catenin.
How does free beta catenin increase risk of developing cancer?
It is able to translocate to the nucleus, where it is able to interact with transcription factors to drive the expression of genes that promote cell proliferation such as MYC.
What are matrix metalloproteinases (MMPs)?
- Enzymes that are normally involved in tissue remodelling as part of wound healing.
- In the stroma surrounding cancer cells, these enzymes are often increased in expression.
How are matrix metalloproteinases involved in metastasis?
- The developing cancer cells produce soluble factors that diffuse through the basement membrane.
- These factors activate the cells of the stroma.
- This increases production of matrix metalloproteinases.
- Matrix metalloproteinases allow the cancer to invade the basement membrane.
How do benign tumours feel different from malignant tumours on palpation?
Why might this be?
- Benign tumours feel soft.
- Malignant tumours feel hard.
- This is because malignant tumour tissue contains many collagen-producing fibroblasts which secrete matrix metalloproteinases.
Define dysplasia.
The presence of cells of an abnormal type within a tissue, which may signify a stage preceding the development of cancer.
When do epithelial cells need to migrate?
How do epithelial cells migrate?
- During wound healing.
- They migrate by a process known as epithelial-mesenchyme transition.