Metastasis Flashcards
What are the 6 stages of metastasis?
Local invasion, intravasion, survival in circulation, extravasion into parenchyma of distant organ, adaptation to new environment and outgrowth of new tumours.
What are two tumour metastasis models?
Linear and parallel
What are the epithelial cell markers?
E-cadherin, Claudin and occludin.
What are mesenchymal cell markers?
N-cadherin, vimentin and fibronectin.
What are epithelial cell characteristics?
Cobblestoned, non-motile/invasive.
What are mesenchymal cell characteristics?
Elongated, motile, invasive.
What is EMT?
Epithelial mesenchymal transition
What drives EMT?
Regulators of epithelial cells: TWIST, SNAI1 and SANI1.
What does MMP-3 do in EMT?
Cleaves E-Cadherin
What happens to E-Cadherin in EMT and what does that cause?
Down regulated leading to less cell connectivity and tight junctions. Increases metastasis.
What factors allow tumour to break through epithelium?
EREG and PTGS2
What does ANGPTL4 do?
Dissciates vascular endothelial cell-cell junctions.
What does PTHRP do?
Enables osteolytic metastases into bones.
Whats are TAMs?
Tumour associated macrophages. Increase metastases.
Do all patients have metastatic tumours?
No some have micro-metastases because they cannot adapt to new environment.
What happen after removal of primary tumour?
Increases in metastatic tumour activity because the primary tumour was secreting suppressor factors to keep micro-metastases dormant.
What suppressor factors can primary tumours secrete?
KAI1, RhoGDIs, JNK and p38.
What does KAI1 do?
Modulatesintegrin and growth receptor signalling.Modulates adhesion and migration.
What does RhoGDIs do?
Negatively regulates MMP2 and MMP9 ECM regulators.
Why cant micro-metastases form tumours in other organs?
Do not have all hallmarks of cancer. Often cannot undergo angiogenesis.
What do JNK and p38 do?
Cell cycle arrest and apoptosis in response to stress signals.
What do ID1 and ID3 do?
Increase metastatic growth, unknown why.
