L03: Tumour Biology Flashcards
What is the definition of metastasis
A tumour that deport discontinuous with the primary tumour
What must a cell be able to do to for metastasis
1) Detach from primary tumour
2) Invade the extracellular matrix by breaking through the basement membrane
3) adhere to the endothelium within the blood vessels
4) extravasate to secondary sites
50 colonise and survive in the secondary organ
How do cells detach from the primary tumour
Adhesion molecules between the cells become downregulated or lost in the cell
Name an adhesion molecule that is downregulated in epithelial cancer
E-Cadherin
What is the role of e-Cadherin
Adhere 2 cells together
What molecule is part of e-Cadherin
Beta catenin
If we lose e-Cadherin what can happen to beta-catenin
Become free
In a normal cell what happens if beta-catenin becomes free and is no longer part of e-Catherine
A complex that involved APC degrades it
What is APC
Tumour supressor gene
Why is free beta catenin dangerous
Floating b catenin can cause it to bind to transcription factors and promote oncogenes transcription
Which oncogenes can become transcribed
MYC
What does MYC or oncogenes lead to
Uncontrolled proliferation
If in a tumour we have loss of e-Cadherin and loss of APC that degrades beta-catenin what can happen
Beta catenin will become freely available to drive oncogenes
Overall what does the loss of e-cadherin and loss of apc show
Knock on effects to the loss of e-Cadherin
After the loss of adhesion what happens to the tumour for it to metastasis
Invade the surrounding connective tissue
What allows the the breakage of basement membrane to have the cell filter to the stroma
Degrading enzymes
What are the degrading enzymes known as
Matrix metalioproteinases (MMPs)
What are MMPs secreted by
Tumour cells
Or
Stroma
What causes the stroma to release MMP’s
Soluble factors produced by pre-malignant dysplastic epithelium
What specific feature within the stroma produces MMPs
Activated fibroblasts
What is epithelial mesenchyme transition
A normal process that is seen in wound healing where epithelial cells are damaged and remaining epithelial cells form to mesenchymal cells to proliferate
What happens to the mesenchymal cells that proliferate in EMT
Reverse back to epithelial morphology
In cancer what happens to the EMT process
Cancer called hijack EMT and enable cancer cells to migrate through the extracellular environment
After the cancer has invaded the stroma what happens next
Intravasation through leaky cell junctions
What happens when the cell has invaded the vasculature
The cells enter smaller capillaries as they flow in the blood and slow down by size restriction
When cells slow down by size restriction what happens to the cell so it become extravated to the secondary site
Adhere to the endothelium through receptor ligand interactions
Is cancer spread to specific sites random
No
Why is the cancer spread not random
Due to the seed and soil hypothesis
What is the seed and soil hypothesis
Metastatic tumours metastasize where the micro-environment is favourable just like a seed will only grow if it lands on fertile soil
Do all circulating tumours give rise to metastatic disease
No because it can become detected and destroyed by the immune system
What allows the secondary site to be favourable for a cancer cell
Metastatic niche
What is a metastatic niche
When the primary tumour cells secrete factors that act on secondary sites to modify the environment and recruiting host immune cells so the cancer cells can proliferate there later on
What type of condition does a tumour usually have
Hypoxia
Which specific region of the tumour is hypoxic
Inside of the tumour i.e necrotic tumour
If tumour cells are hypoxic how do they respond
By initiating angiogenesis
What is angiogenesis
New formation of blood vessels
Which transcription factor controls angiogenesis
HIF
What does angiogenesis allow
Supplies oxygen and nutrients to the necrotic tumour and takes away its waste
Increases survival
Apart from angiogenesis what does the hypoxic response also do
Switch from areobic to anaerobic respiration
If anaerobic respiration is occuring where does most of the energy come from
Glycolysis
What does glycolysis involve
Upregulating glucose
How can we visualise tumours using the knowledge on glycolic switch
1) Give a patient glucose analogue called flurodeoxyglucose
2) screen with a PET scan
What does glycosis of tumour cells enable
Compete with normal cells for scarce glucose supply
If cancer cells compete for glucose with normal cells, what happens to normal cells
Cell death
What by-product is produced as a result of anaerobic respiration
Lactic acid
What can lactic acid do to the environment that leads to further death of normal cells
Acidify it
