Invasion and Metastasis Flashcards
5 steps of cell metastasis
Penetrate vessels
Release into circulation
Survive in circulation
Arrest at organs
Penetrate vessels
Formation of secondary tumour
Colonisation
How does EMT allow metastasis?
Cancer cells become long and thin to invade basement membrane
Epithelial cell traits
Fixed cell polarity
Cell adhesion (to each other and to ECM)
Stationary
Mesenchymal cell traits
No cell polarity
Loss of cell adhesion
Ability to migrate and invade
Describe cadherin switching
Unlike epithelial cells, mesenchymal cells have low levels of E-cadherin and high levels of N-cadherin
What are some transcription factors that cause EMT?
SNAl1 - invasive ductal carcinoma
Twist - melanoma, neuroblastoma
How do transcription factors normally work?
Tightly controlled during development then permanently switched off
Which gene is switched on to develop chemotherapy resistance in cells?
FGF1
What are the classifications of matrix degrading proteases?
serine-
cysteine-
aspartyl-
metallo-
MMP production
MMPs are synthesised as inactive proenzymes and activated by the cleavage of a propeptide.
Gene control of MMPs
MMPs can be switched on and off quickly by genes
How do cancer cells survive in circulation?
Microthrombus
(cell protects itself with platelet shield and rolls through blood vessel)
How do cancer cells move along the membrane?
- switch on proteins at leading edge
- switch off proteins at lagging edge
actin polymerization at the lagging end end protrudes lamellipodium at the leading end
Examples of cell surface receptors that allow cancer cells to adhere to the membrane
CXCR4 and CXCR7
Integrins
Form contacts with actin cytoskeleton
What regulates cell motility?
Rho
Rac
Cdc42
How can a complex primary tumour have simple metastasis?
Only one clone can metastasise
What is the most likely to allows dormancy and reawakening of primary cancer?
Senescence is probably not terminal
What can senescent cells release when they come back?
chemokines, cytokines and proteases
Phenotypic plasticity describes reversible phenotypes. What is this linked to?
disease progression and treatment resistance
Biomarkers in cell motility
Cell is made more motile by increasing expression of specific protein
Factors that encourage cancer cells to metastasise to a specific organ
Growth factors
Adhesion sites
Chemotaxis
ECM environment
