Lecture 15 - Neoplasia 2 Flashcards
What is the definition of Invasion?
Breach of the basement membrane with progressive infiltration and destruction of the surrounding tissues
What is Metastasis?
Spread of tumour to sites that are physically discontinuous from the primary tumour
What type of tumours can invade basement membranes?
Malignant tumours
What are the basic steps to metastasis?
Grow and invade at primary site (Initiation, promotion and progression)
Enter a transport system and lodge at a secondary
Grow at the secondary site to form a new tumour
What 3 key events happen in invasion involving a carcinoma cell?
Altered adhesion
Stromal proteolysis
Motility
What is epithelial to mesenchymal transition?
When the invading carcinoma cell takes on phenotype more similar a to the mesenchymal/stromal cells around it
What happens in the adhesion stage of invasion?
Reduced E-cadherin expression
Changes in Integrin expression
What are E-Cadherins?
Cell to cell adhesions
What are integrins?
Cell to basement membrane adhesions
What is the function of the Adhesion stage of invasion?
Frees carcinoma cells so they can move and invade the basement membrane
What happens in the stromal proteolysis stage of invasion?
Proteases released which degrade the basement membrane and stroma allowing for invasion
What happens in the Motility stage of Invasion?
Changes in the actin cytoskeleton of the carcinoma cell allowing it to move and invade
How do malignant cells take advantage of nearby non neoplastic cells?
Stimulate the stroma to produce growth factors and proteases
How do malignant cells spread to distant cells?
Blood vessels (Haematogenous spread)
Lymphatic vessels
Fluid in body cavities (transcoelomic spread)
How do malignant cells normally access nutrient?
Invade blood vessels
Create their own blood vessels
What is failed colonisation?
When a metastasis fails to establish and grow
How can dormant malignant cells occur?
Malignant cells lodge at secondary sites as tiny undetectable cell clusters that fail to grow