Invasion and metastasis

Question 1

what is metastasis

Answer 1

when tumour cells leave the primary tumour to travel to a distant site

Question 2

what systems do tumour cells migrate through?

Answer 2

blood or lymth

Question 3

TF cancer often involves drastic shape changes of cells

Answer 3

true- drastic

Question 4

what is epithelial mesenchymal transition?

Answer 4

the conversion of a epithelial cell to non polarised motile spindle shaped cell resembling a fibroblast

Question 5

what is epithelial mesenchymal transition influenced by?

Answer 5

tume me AT THE EDGE OF THE TUMOUR IN CONTACT WITH THE TUMOUR STROMA

Question 6

5 STAGES OF METASTASIS?

Answer 6

1. invasion
2. intravasation
3. transport
4. extravasation
5. angiogenesis

Question 7

explain invasion?

Answer 7

stage at which the dissociated tumour cells infiltrate to the surrounding storm and invade through the membrane which has the blood and lymphs

Question 8

explain intravasation

Answer 8

dissociated tumour cells get into the basculature

Question 9

what must the tumour cells do before undergoing intravasiation?

Answer 9

successfully crossed the extracellular matriculates

Question 10

2 ways cells move in the circulatory systems

Answer 10

actively by motility of be passively carried with fluid flow

Question 11

what is anoikis

Answer 11

a form of apoptosis which is triggered by detachment of a solid substrate

Question 12

what do some cells need to do in the circulatory system to avoid anoikis

Answer 12

anchorage to solid substrate

Question 13

do metastatic cells tend to undergo anoikis?

Answer 13

they tend to be more resistant than non-metastatic cells

‘anchorage independent’

Question 14

explain extravasation

Answer 14

the cells actively leaving the vasaclature

Question 15

normal cells have a _____ level of E cadherin and a _____ level of N cadherin

Answer 15

high

low

Question 16

cancer cells have a _____ level of E cadherin and a _____ level of N cadherin

Answer 16

low

high

Question 17

2 features of mesenchymal cells compared to normal re polarity and adhesion

Answer 17

mesenchymal cells have no cell polarity and have a loss of cell adhesion

Question 18

how are mesenchymal tumour cells able to become free from cell adhesions?

Answer 18

degradative enzymes are produced by them or immune cells to degrade the matrix and facilitate invasion

Question 19

4 enzymes implicated in tumour cell invasion?

Answer 19

serine proteinases plasmin
plasminogen activator
cathepsin b
metal dependent proteinases of the matrix metalloproteinase MMP fairy

Question 20

epithelial cell cell interactions are mediated primarily by?

Answer 20

cadherins

Question 21

what are cadherins

Answer 21

transmembrane glycoproteins

recognise and bind to molecules of the same kind in adjacent cells

Question 22

what is the rate limiting step in the metastatic process?

Answer 22

intravasation

Question 23

what is transendothelial migration?

Answer 23

tumour cells attach to the vasculature endothelial wall to create enough space to get into the vasculature

Question 24

what protects the cancer cells from shear stress in the circulatory system?

Answer 24

thrombus formation around the tumour cells

Question 25

what else does thrombus formation around the cancer cell do to help the tumour

Answer 25

secrete angiogenic growth factors to support secondary establishment of tumours

Question 26

role of P-selectin when the tumour cell is in the blood

Answer 26

helps them evade recognition by immune | released by leukocytes and platelets which bridge between endothelial cells and metastatic tumour cells

Question 27

explain extraversion process

Answer 27

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

Question 28

what happens to the micro thrombus which forms around a cancer cell which is undergoing extravasation

Answer 28

gets dissolved by proteases

Question 29

what are the most common sites of metastasis

Answer 29

lung and liver as most tumour cells enter the vasculature in small veins or capillaries

Question 30

does metastasis happen by chance?

Answer 30

no it only happens when the tumour cells have metastatic ability and the organs have growth advantage they must both be compatible

Question 31

what is the seed and soil hypothesis

Answer 31

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.

Question 32

role of matrix metalloproteases?

Answer 32

degrade components of the ECM facilitating angiogenesis, tumour invasion and metastasis also activate signalling molecules ee.g. vascular GF

Question 33

how do MMPs modulate the interactions between tumour cells?

Answer 33

by cleaving E cadherin between tumour cells and the ECM

Question 34

why is MMP a good target for cancer therapies?

Answer 34

as they have multiple functions

Question 35

what does expression of N-cadherin do? what is the correlated with?

Answer 35

provokes E-cadherin down regulation which is correlated with increased invasion and metastatic progression

Question 36

how can we target N-cadherin in cancer?

Answer 36

antagonise | monoclonal antibody against

Question 37

what happens to platelets when they adhere to tumour cells in the blood?

Answer 37

they get activated which: promotes platelet Shape change intergrin activation release of biologically active molecules (ATP,ADP,MMP, TFG-b, gf)

Question 38

What do the molecules released by activated intergrins when tumour cells bind to platelets promote?

Answer 38

ATP, ADP, MMP-2, TGF-b, GF they cause platelets aggregation epithelial mesenchymal transition angiogenesis

Question 39

what causes intergrin activation when tumour cells and platelets interact?

Answer 39

activated upon Tallinn and kindling binding to the intracytoplasmic domain of the b3 chain

Question 40

what are selectins? where are they found

Answer 40

adhesion receptors on leukocytes, vascular endothelial cells and cancer cells they're bad as they facilitate the extravasation of cancer cells

Question 41

what can inhibitors of P-selectin do?

Answer 41

prevent interactions of platelets with cancer cells | = anti-metastatic activity

Question 42

how does CD44 promote metastasis

Answer 42

lymphocyte honing receptor by forming a complex with MMP-9 concentrates the MMP-9 at the surface

Question 43

what can we do to CD44 in cancer therapy?

Answer 43

block it