Flashcards in Behaviour of tumours Deck (48)
What is the difference between invasion and metastasis?
Invasion if of local tissues and destroys normal tissue, at this point the cancer is still a local disease
Metastasis is the spreading from the site of origin to distant sites and forming new tumours in these areas
At this point the cancer has become a systemic disease
How many cancer patients are killed by metastatic disease?
What proportion of breast cancer patients are killed by metastatic disease?
What proportion of lung cancer patients are killed by metastatic disease?
What proportion of patients with basal cell carcinoma are killed by metastatic disease?
By what basic mechanisms do tumour cells start to invade local tissues?
1) Increased motility
2) Decreased adhesion
3) Mechanical pressure
4) Production of proteolytic enzymes
What are the 2 classes of adhesion molecule which are lost in malignant cells?
Cell to cell adhesion molecules - cadherins
Cell to matrix adhesion molecules - integrins
What changes occur leading to a reduction in adhesion of malignant cells?
Mutation of E-cadherin in malignant cells leads to loss of cell-cell adhesion and contact inhibition
Changes in integrin expression in malignant cells lead to decreased cell-matrix adhesion
What is meant by the epithelial-mesenchymal transition?
Occurs in malignancy epithelial cells gain mesenchymal properties and can invade and migrate. Eg. epithelial cells are tightly connected polarised and tethered whereas mesenchymal cells are loosely connected and able to migrate
What is the role or proteolytic enzymes in invasion?
They are matrix metalloproteinases produced by the malignant cells which degrade the extracellular matrix
Interstitial collagenases are produced by malignant cells, what do they degrade?
Collagen types I, II, III
Gelatinases are produced by malignant cells, what do they degrade?
Collagen type IV, gelatin
Stomolysins are produced by malignant cells, what do they degrade?
Collagen type IV, proteoglycans
What is the main constituent of extracellular space?
Are metalloproteinases produced by healthy cells?
Yes, they play a role in normal tissue regulation and are balanced by tissue inhibitors of metalloproteinases
How does the balance between metalloproteinases and inhibitors change in malignancy?
Increase in metalloproteinases and decrease in tissue inhibitors of metalloproteinases so they are no longer balanced, this favours tissue breakdown
What is the role of metalloproteinases in normal tissue regulation?
Needed to mop up collagen and remodel tissues etc.
How does mechanical pressure contribute to invasion?
Uncontrolled proliferation forms a mass
Pressure occludes vessels
Get pressure atrophy
Tumour spreads along the line of least resistance
Name the 4 routes of metastasis?
4) Implantation - spillage of tumour during biopsy/surgery etc.
Give 4 cancers which commonly metastasize by the blood route?
What is meant by the transcoloemic route of metastasis?
Across peritoneal, pleural, pericardial cavities or in CSF
Name the 5 stages of metastasis?
1) Detachment invasion
2) Intravasation (invasion of cancer cells through the basement membrane into blood vessels or lymphatics)
3) Survival against host defences
4) Adherence extravasation (from the lymph or blood vessels into surrounding tissues)
5) Growth (involving angiogenesis)
Carcinomas commonly spread by which route?
Sarcomas commonly spread by which route?
Bone metastases are common in what 5 cancers?
Ovarian cancer commonly spreads by which route?
Brain and adrenal metastases commonly come from which cancer?
What 2 types of bone metastases can occur?
Bone metastases can by:
What are the 2 different theories about patterns of metastasis?
1) Mechanical hypothesis - pattern in dictated by anatomy eg. lymphatic drainage
2) Seed and soil hypothesis - malignant cells can travel anywhere, but 'seeds' are more likely to grow on good soil - ie organs with a good tissue environment for malignant cells