mechanisms of tumour progression, invasion and metastasis

Question 1

what can cause chromosomal instability in sporadic cancers

Answer 1

growth
invasiveness
metastasis

Question 2

what is the growth characteristic of malignant tumours

Answer 2

have unlimited growth potential as long as an adequate blood supply can prevent tumor hypoxia

Question 3

what is the invasiveness characteristic of malignant tumour

Answer 3

invasion of surrounding tissue (when they have contact with vascular or lymphatic vessels)

Question 4

what is the metastatic characteristic of malignant tumours

Answer 4

spread of tumour cells from primary site to secondary tumours at other sites

Question 5

what is the commonest cause of death in cancer patients

Answer 5

tumour metastasis

Question 6

what is microsatellite instability

Answer 6

microsatellites are 2-5bp repeats - bc thousands of repeats =difficult to replicate by DNA polymerase .’. it can slip and insert too many/few bases.
if not repaired by mismatch repair systems can cause downstream genes to move out of place .’. can render genes non-functioning

Question 7

What causes hereditary nonpolyposis colorectal cancer

Answer 7

loss of mismatch repair function

Question 8

how do cancerous cells silence TSG and why

Answer 8

Methylation of the promoter or enhancer means expression can be stopped.
e.g. silencing CDK inhibitors so CDK can phosphorylate and progress the cell cycle

Question 9

how do cancerous cells silence TSG and why

Answer 9

Methylation of the promoter or enhancer means expression can be stopped.
e.g. silencing CDK inhibitors so CDK can phosphorylate and progress the cell cycle

Question 10

what is meant by cancer dissemination

Answer 10

cancer spreading/ metastasising

Question 11

how do tumours disseminate

Answer 11

tumour cells need access to blood supply. invasate into blood/lymph and transported in circulation. cells arrest in microvessels of various organs and extravasate into tissue where it can from a micrometastasis. secondary tumour requires a blood supply itself in order to continue growing into a macrometastasis

Question 12

what is intravasation

Answer 12

the invasion of cancer cells through the basal membrane into a blood or lymphatic vessel. done in order to disseminate

Question 13

what is intravasation

Answer 13

the invasion of cancer cells through the basal membrane into a blood or lymphatic vessel. done in order to disseminate

Question 14

the process of tumour dissemination efficient?

Answer 14

intravasation and extravasation is v efficient. What makes overall dissemination inefficient is that tumours cannot grow beyond 2mm without having own blood supply so need to set up own blood supply

Question 15

what factors can (some) tumours produce to stimulate angiogenesis

Answer 15

Vascular endothelial growth factor (VEGF)
Fibroblast Growth factor (FGF-2)
Transforming growth factor (TGF-beta)
Hepatocyte growth factor/scatter factor

Question 16

what are the 3 ways in which the cancerous tumour invade into the local tissues

Answer 16

mechanical pressure of rapidly proliferating tissue
increased motility of malignant cells
increased production of degradative enzymes by tumour cells

Question 17

how do carcinoma epithelial cells change its characteristics to transition into mesenchymal cells

Answer 17

loss of: epithelial cell shape and cell polarity, - Cytokeratin intermediate filament expression, - Epithelial adherens junction protein
tumour cells acquire: fibroblast-like shape &motility, invasiveness, Vimentin intermediate filament expression, Mesenchymal gene expression, Protease secretion

Question 18

what are e-cadherins (epithelial cadherins)

Answer 18

involved in homotypic adhesion, Ca2+ dependent, can bind b-catenin,

Question 19

what happens to e-cadherins in tumours

Answer 19

in epithelial tumours they are replaced by integrins

Question 20

what are integrins

Answer 20

(common in carcinoma)
- exist as heterodimer on cell surface (a & b), heterotypic adhesion molecules, allow cell migration by progressively binding proteins as it moves through

Question 21

what are integrins

Answer 21

(common in carcinoma)
- exist as heterodimer on cell surface (a & b), heterotypic adhesion molecules, allow cell migration by progressively binding proteins as it moves through

Question 22

what releases proteases in cancers

Answer 22

cancerous tumour cells as well as normal stromal cells that have got caught up in the tumour

Question 23

what do normal stromal cells release

Answer 23

pro-uPA (urokinase plasminogen activator)

Question 24

what is the role of pro-uPA in cancer and what cells release it

Answer 24

released by normal stromal cells that are incorporated into tumour. binds to receptors expressed on cancerous cells and results in activation of uPA. uPA activates plasminogen to plasmin -> activates MMPs in the ECM to degrade the ECM .’. enables invasion and release matrix bound angiogenic factors

Question 25

what are examples of stromal cells

Answer 25

macrophages, mast cells, fibroblasts

Question 26

what can stromal cells release

Answer 26

angiogenic factors, growth factors, cytokines, proteases that have important effects on tumour progression.

Question 27

what are MMPs

Answer 27

matrix metalloproteins

Question 28

what does the extent of proteolysis depend on

Answer 28

relative amounts of proteinase and proteinase inhibitors.

most tissues have high TIMPs TIMPS (Tissue inhibitors of Metalloproteinases)

Question 29

what determines the pattern of tumour spread

Answer 29

mechanical hypothesis

seed and soil hypothesis

Question 30

what is the mechanical hypothesis of tumour spread

Answer 30

anatomical factors =common patterns, eg blood and lymphatic system pathways that supply the tumour and then subsequent entrapment in capillary beds.

Question 31

what is the seed and soil hypothesis of tumour spread

Answer 31

tumour cells have specific adhesion proteins .’. can arrest &invaginate at specific sites in target organ. these target organs =a favourable environment for tumour to colonise.

Question 32

what process is key to survival and growth of a tumour

Answer 32

angiogenesis.

hypoxia drives it