Tumour Progression and Metastasis Flashcards
Metastasis can be ___ but never really ___
Metastasis can be managed but never really cured.
How many changes are needed for metastasis?
A lot, because a cell needs to be able to move, and then grow where it shouldn’t be
80% of breast cancers metastasise to bone, why is that?
Because they tend to have a master regulator of bone development that is normally only found in bone, expressed in breast
What’s the biggest risk factor for cancer?
age
Why is age the biggest risk factor for cancer?
Lost the capcacity to repair DNA.
Have accumulated mutations.
Reduced immune surveillance
Explain the stepwise model of mutations leading to metastasis
Sequential mutations that accumulate. Removing a negative cell cycle regulator, activating a positive regulator, inhibiting cell death, all leading to transformation
Tumour cells affect the environment and…
Create a tumour microenvironment, and the environment made then affects the cells.
If you completely remove a tumour, why can that not be enough to cure?
Cells may have metastasised and then be dormant. Can be reactivate through any number of things
What transition does a cell need to go under to metastasise?
Epithelial to mesenchymal transition, and then back again
Name the steps in carcinoma progression
Hyperplasia, carcinoma, invasive carcinoma, metastatic carcinoma
Name some of the hallmarks of cancer
Genome instability, resist cell death, avoid immune destruction, access vasculature, evade growth supressors, sustained proliferative signalling, phenotypic plasticity, deregulated metabolism
What is Transcolemic spread?
Where a cancer penetrates the peritoneum cavity, e.g. ovary -> liver
What is haematogenous spread?
Cancer enters blood vessels, can reach many distant locations
What is lymphatic spread?
Cancer goes to lymph nodes. Lymphatic system is large network that drains much of the body. Can lead to Haematogenous spread.
What is the seed and soil theory?
Cancer cells die easily in the wrong environment. They need a good, similar location to land in.
What does the theory contrary to the seed and soil theory say?
That cells land where they naturally drain to.
What are the early events of metastasis?
Loss of tissue organisation, cells lose some identity, detach from where they are and then breach the basement membrane.
Once a cancer cell has breach the basement membrane, what else do they need to cross?
The stroma and endothelial layer
How do adhesion changes promote the movement of cancer cells?
Ability to invade the stroma and endothelial lining. Can survive in inappropriate contexts. Can enter circulation.
What was James Ewing’s big idea?
Circulation predicting the site of metastasis. Cells travel in clumps and often get entrapped in the first vascular bed they come across.
Cells typically have a top and bottom, this is called? certain cell types have it disrupted in cancer causing?
Polarisation.
Basal cell carcinoma, squamous cell carcinomas. If any more disruption, would become invasive.
How do cells stay in their normal place? What adhesion is there?
Cell-Cell adhesion - E-cadherin and desmoplakin.Desmosomes are intermediate filament.
Gap junctions.
Cell-ECM adhesion. - Integrins, Laminin (hemidesmosome), focal adhesions
In an EMT, what happens to E-cadherin?
Replaced by N-cadherin.
Lost by TFs, degradation, phosphorylation, methylation of gene etc.
How can cells sometimes file down a path into the blood?
If a cell gets the ability to make collagenases it will carve out a path.
