Cancer 2 Flashcards
What do tumour cells need to do in order to spread?
(1 mark)
Break cell-cell and cell-ECM attatchment
What is Organotropism and why can it happen?
- Where cancer spreads to specific part of the body.
- May be due to:
- direction of blood flow
- so tumour cells can get trapped in capillary beds
What is the ‘Seed and soil hypothesis’?
Apply it to a specific tumour.
- The need to match with optimum environment to grow - by Paget
- Kidney tumour likes to grow in the thyroid gland
What is a pre-metastic niche? Give an example. (2 marks)
- When a distant site is prepared by molecules released by tumour
- E.g. prostrate cancer secretes molecules that breakdown bone and prepapre it for metastic cells
What happens in each of the stages below: (6 marks)
- Invasion
- Intravasion
- Transport
- Extravasion
- Metastasis
- Invasion: introduction of EMT to get mobile cells
- Intravasion: tumour into blood vessel AKA circulating tumour cell. Only need one to survive to form a metastatic tumour
- Transport: transport in blood stream
- Extravasion: exit blood and swithc on angiogenesis can grow exponentially
- Metastasis: metastatic colonisation and angiogenesis
What is an ‘invadeapodia’ and how does it assist the formation of tumour cells? How is it formed? (2 marks)
Secretes molecules that breaks down basement membrane to allow tumour cells to get through.
Formed by cells breaking through basement membrane to underlying tissue
What is metastatic colonisation? (3 marks)
- Establishment of a progressively growing tumour at a distant site
- Involves formation of new blood vessels - an essential process to provide nutrients and oxygen
What does a tumour need to produce to degrade the basement membrane?
Proteases and enzymes whihc degrade the peptide bonds between amino acids
Why is Src a good target for drug therapy? (2 marks)
- In tumours Src helps mediate breakdown of cell:cell and cell:ECM contacts.
- Targeting this will decrease motility of tumour
What does EMT stand for? What does it do? (5 marks)
- Epithelial mesenchymal transition (EMT)
- Static epithelial cells transformed into mesenchymal cells
- Stroma make signals to drive EMT - cancer cells hijack TGF-ß to make more mobile
- Loss of cell adhesion molecules
- Increase in mesenchymal markers
- Use of SNAIL and TWIST
What do SNAIL and TWIST do in metastasis? (5 marks)
- Both control genes needed to trigger EMT
TWIST:
- Key regulator of metastasis - inhibit and see loss in metastasis steps
- TF activated from receptor kinase
SNAIL:
- Binds to E box sequences in epithelial genes and recruits polypeptide
- So causes histone modifications and epigenetic regulation to repress gene expression
What are the EMERGING hallmarks of cancer? (2 marks)
- Ability of tumour cell to completely reprogramme metabolism
- Ability cancer cells to avoid being destroyed
What is the Warburg effect? (3 marks)
- Increase in rate of glucose uptake and preferential production of lactate despite being in the presence of oxygen
- Cancer cells do this as they need energy much quicker than normal cells for their rapid growth
Why do cancer cells utilise aerobic glycolysis? (2 marks)
- Angiogenesis in tumour is quite leaky so if were not to use aerobic glcolysis a lot of it would be hypoxic (the ferment)
- Tumour cells have dependency on glucose
What is immune surveillance?
Where the immune system can recognise and kill tumour cells. People on immunosuprressants after organ transplant more susceptible to cancer
How does the immune system recognise and kill cancer cells?
(4 marks)
- Cancer cells have cancer specific antigens
- Cell dies, it is presented to T cell so can recognise the antigen
- T cell infiltrates the tumour and binds to tumour cells and kills it
- Thus releasing more antigen for recognition
How does a T cell kill a cancer cell?
- Injects granzyme and its target is effector caspases - granzyme will cleave these into their active form
- Or bind to death ligand on cell surface which locks onto death receptors and triggers apoptosis
How can cancer cells negatively affect T cell priming?
(5 marks)
(Think of avoiding immune destruction)
- Can decrease tumour antigens
- Cause down regulation of antigen presenting molecules
- Over express main checkpoint proteins
- Tumour produces lots of PD-L1 to trick T cell into thinking it’s dying when it actually isn’t
- Cancer cells an change immune cells recruited to their microenvironment e.g. anti-inflammatory cytokines
PD-L1 is a ‘programmed death’ ligand
What do macrophages produce that the tumour can use as growth molecules?
Cytokines
How is chronic inflammation related to cancer? (1 mark)
Lots of chronic inflammation present in disregulated fat - increased amount of cytokines in inflammation which can be sed as a growth tool by tumours e.g. Type 2 diabetes
What benefit do cancer stem cells have?
- Infinite replication potential as can maintain telomere length (doesn’t have to break off)
- Self-renew and differentiate into anything
What is present at the bottom of the crypts of villi in the intestine? How does this contribute to carcinoma formation?
(2 marks)
- Stem cells that migrate and differentiate at top of crypt where they die by apoptosis
- Secretory epithelial cells more prone to mutations and carcinoma formation
What are cancer stem cells responsible for? (2 marks)
Tumour plasticity
Migratory abilities
What is ‘heterogeneity in tumours’? (1 mark)
- Due to cancer stem cells, can renew themselves adn give rise to cells that differentiate into different types of cells
- Good target for drug therapy
