Invasion and metastasis Flashcards
what is metastasis
when tumour cells leave the primary tumour to travel to a distant site
what systems do tumour cells migrate through?
blood or lymth
TF cancer often involves drastic shape changes of cells
true- drastic
what is epithelial mesenchymal transition?
the conversion of a epithelial cell to non polarised motile spindle shaped cell resembling a fibroblast
what is epithelial mesenchymal transition influenced by?
tume me AT THE EDGE OF THE TUMOUR IN CONTACT WITH THE TUMOUR STROMA
5 STAGES OF METASTASIS?
- invasion
- intravasation
- transport
- extravasation
- angiogenesis
explain invasion?
stage at which the dissociated tumour cells infiltrate to the surrounding storm and invade through the membrane which has the blood and lymphs
explain intravasation
dissociated tumour cells get into the basculature
what must the tumour cells do before undergoing intravasiation?
successfully crossed the extracellular matriculates
2 ways cells move in the circulatory systems
actively by motility of be passively carried with fluid flow
what is anoikis
a form of apoptosis which is triggered by detachment of a solid substrate
what do some cells need to do in the circulatory system to avoid anoikis
anchorage to solid substrate
do metastatic cells tend to undergo anoikis?
they tend to be more resistant than non-metastatic cells
‘anchorage independent’
explain extravasation
the cells actively leaving the vasaclature
normal cells have a _____ level of E cadherin and a _____ level of N cadherin
high
low
cancer cells have a _____ level of E cadherin and a _____ level of N cadherin
low
high
2 features of mesenchymal cells compared to normal re polarity and adhesion
mesenchymal cells have no cell polarity and have a loss of cell adhesion
how are mesenchymal tumour cells able to become free from cell adhesions?
degradative enzymes are produced by them or immune cells to degrade the matrix and facilitate invasion
4 enzymes implicated in tumour cell invasion?
serine proteinases plasmin
plasminogen activator
cathepsin b
metal dependent proteinases of the matrix metalloproteinase MMP fairy
epithelial cell cell interactions are mediated primarily by?
cadherins
what are cadherins
transmembrane glycoproteins
recognise and bind to molecules of the same kind in adjacent cells
what is the rate limiting step in the metastatic process?
intravasation
what is transendothelial migration?
tumour cells attach to the vasculature endothelial wall to create enough space to get into the vasculature
what protects the cancer cells from shear stress in the circulatory system?
thrombus formation around the tumour cells
what else does thrombus formation around the cancer cell do to help the tumour
secrete angiogenic growth factors to support secondary establishment of tumours
role of P-selectin when the tumour cell is in the blood
helps them evade recognition by immune
released by leukocytes and platelets which bridge between endothelial cells and metastatic tumour cells
explain extraversion process
cell is trapped physically in the capillary
with minutes a large number of platelets attach to the cell forming a micro thrombus
the cancer cell pushes endothelial cells aside and achieves direct contact with the underlying capillary basement membrane
proteases dissolve the microthrombus within a day
the cancer cell proliferates IN the lumen of the capillary
within a few days the cancer cells break through the capillary basement membrane and invade the surrounding tissue
what happens to the micro thrombus which forms around a cancer cell which is undergoing extravasation
gets dissolved by proteases
what are the most common sites of metastasis
lung and liver as most tumour cells enter the vasculature in small veins or capillaries
does metastasis happen by chance?
no it only happens when the tumour cells have metastatic ability and the organs have growth advantage
they must both be compatible
what is the seed and soil hypothesis
metastasis happens only when:
o The seed (the tumor cells with metastatic ability)
o The soil (the organs or tissues providing growth advantage to seeds) are compatible.
role of matrix metalloproteases?
degrade components of the ECM facilitating angiogenesis, tumour invasion and metastasis
also activate signalling molecules ee.g. vascular GF
how do MMPs modulate the interactions between tumour cells?
by cleaving E cadherin between tumour cells and the ECM
why is MMP a good target for cancer therapies?
as they have multiple functions
what does expression of N-cadherin do? what is the correlated with?
provokes E-cadherin down regulation which is correlated with increased invasion and metastatic progression
how can we target N-cadherin in cancer?
antagonise
monoclonal antibody against
what happens to platelets when they adhere to tumour cells in the blood?
they get activated which:
promotes platelet Shape change
intergrin activation
release of biologically active molecules (ATP,ADP,MMP, TFG-b, gf)
What do the molecules released by activated intergrins when tumour cells bind to platelets promote?
ATP, ADP, MMP-2, TGF-b, GF
they cause platelets aggregation
epithelial mesenchymal transition
angiogenesis
what causes intergrin activation when tumour cells and platelets interact?
activated upon Tallinn and kindling binding to the intracytoplasmic domain of the b3 chain
what are selectins? where are they found
adhesion receptors on leukocytes, vascular endothelial cells and cancer cells
they’re bad as they facilitate the extravasation of cancer cells
what can inhibitors of P-selectin do?
prevent interactions of platelets with cancer cells
= anti-metastatic activity
how does CD44 promote metastasis
lymphocyte honing receptor
by forming a complex with MMP-9
concentrates the MMP-9 at the surface
what can we do to CD44 in cancer therapy?
block it
