Tumour Angiogenesis, Invasion And Metastasis

Question 1

What are the characteristics of malignant tumours?

Answer 1

Growth
Invasiveness
Metastasis

Question 2

What is the growth potential of a malignant tumour?

Answer 2

Unlimited as long as adequate blood supply is available

Question 3

What is the invasiveness characteristic of a malignant tumour?

Answer 3

Migration of tumour cells into the surrounding stroma where they disseminate

Question 4

What is the metastatic characteristic of a malignant tumour?

Answer 4

Spread of tumour cells from the primary site to form secondary tumours at other sites in the body

Question 5

What are the key steps in cancer progression?

Answer 5

Transformation
Angiogenesis
Motility and invasion
Metastasis

Question 6

What is transformation of a cancer?

Answer 6

Extensive mutagenic and epigenetic changes followed by clonal selection

Question 7

What is angiogenesis?

Answer 7

New blood vessel formation from pre-existing vessels

Question 8

What is vasculogenesis?

Answer 8

Formation of new blood vessels from progenitors

Question 9

What are the types of angiogenesis?

Answer 9

Developmental (vasculogenesis)
Normal angiogenesis
Pathological angiogenesis

Question 10

What is pathological angiogenesis?

Answer 10

Tumour angiogenesis

Seen in ocular and inflammatory disorders

Question 11

When does normal angiogenesis occur?

Answer 11

Wound repair
Placenta furing pregnancy
Cycling ovary

Question 12

What is the max. Size of a tumour without their own blood supply?

Answer 12

1-2mm^3 without their own organ blood supply

Question 13

What are the steps in tumour angiogenesis?

Answer 13

Small tumour gets big enough to need its own blood supply
Tumour switches on expression of angiogenic genes/factors
New blood vessels grow in and around the tumour, increasing the delivery of oxygen

Question 14

What is a strong stimulus for tumour angiogenesis?

Answer 14

Hypoxia

Question 15

What genes are involved in angiogenesis?

Answer 15

Vascular endothelial growth
Glucose transporter 1
Urokinase plasminogen activator receptor
Plasminogen activator inhibitor 1

Question 16

What does plasminogen activator 1 cause?

Answer 16

Invasion and metastasis

Question 17

What factors stimulate the directional growth of endothelial cells (angiogenic factors)?

Answer 17

Vascular endothelial growth factor
Fibroblast growth factor 2
Placental growth factor
Angiopoietin 2

Question 18

What are the angiogenic factors secreted by?

Answer 18

Tumour cells or components of the extracellular matrix

Question 19

What does VEGF do?

Answer 19

activates cell survival, vascular permeability, gene expression and cell proliferation

Question 20

What do you loose in the epithelial-mesenchymal transition?

Answer 20

Epithelial shape and polarity
Cytokeratin intermediate filament expression
Epithelial adherens junction position

Question 21

What do you gain in the epithelial-mesenchymal transition?

Answer 21

Fibroblast-like shape and motility
Invasiveness
Vimentin intermediate filament expression
Mesenchymal gene expression 
Protease secretion

Question 22

What proteases are secreted in the epithelial-mesenchymal transition?

Answer 22

MMP-2 and MMP-9

Question 23

What causes the loss of epithelial shape and cell polarity in the epithelial-mesenchymal transition?

Answer 23

Beta-catenin and cloudin-1

Question 24

What causes the loss of epithelial adherens junction position in the epithelial-mesenchymal transition?

Answer 24

E-cadherin

Question 25

What increases the gain of mesenchymal gene expression in the epithelial-mesenchymal transition?

Answer 25

Fibronectin, PDGF receptor, alpha 5 beta 6 integrin

Question 26

What are E-cadherins?

Answer 26

Homotypic adhesion molecules

Question 27

What are E-cadherins dependant on?

Answer 27

Calcium

Question 28

What do E-cadherins inhibit?

Answer 28

Invasiveness

Question 29

What does E-cadherin bind to?

Answer 29

Beta-katenin

Question 30

What is contact inhibition?

Answer 30

Once cells have bound to other cells with the same cadherin, it signals for them not to migrate or proliferate

Question 31

What forms a tumour mass?

Answer 31

When E-cadherin is lost in tumours, so you loose contact inhibition and cells grow on top of each other and proliferate

Question 32

What factors are released by stromal cells?

Answer 32

Angiogenic factors, growth factors, cytokines and proteases

Question 33

What does the tumour activation of urokinase-type plasminogen activator result in?

Answer 33

Plasmin production

Question 34

What does plasmin activate?

Answer 34

Matrix metalloproteases

Question 35

What do matrix metalloproteases do?

Answer 35

degrade extracellular matrix release matrix-bound angiogenic factors Which allows invasion

Question 36

What is an example of a matrix bound angiogenic factor?

Answer 36

Transforming growth factor-beta1

Question 37

What are the common sites of metastasis for breast cancer?

Answer 37

Lung Liver Brain Bone

Question 38

What are the hypotheses for pattern of tumour spread?

Answer 38

Mechanical hypothesis Seed and soil hypothesis Genetic alterations acquired during disease progression

Question 39

What is the mechanical hypothesis for tumour spread?

Answer 39

Anatomical considerations like blood and lymphatic systems and entrapment in capillary beds

Question 40

What is the seed and soil hypothesis for tumour spread?

Answer 40

Specific adhesions between tumour cells and endothelial cells in the target organ, creating a favourable environment in the target organ for colonisation

Question 41

What tumour processes can be targeted to inhibit cancer?

Answer 41

Tumour angiogenesis Cell motility Invasion

Question 42

What is avastin?

Answer 42

Monoclonal antibody drug that targets anti-angiogenesis

Question 43

What types of cancer is avastin approved for?

Answer 43

Colorectal, lung, kidney, ovarian

Question 44

How does avastin work?

Answer 44

Binds to VEGF and prevents it from binding to VEGF receptors on endothelial cells

Question 45

What are the common sites of metastasis for breast cancer?

Answer 45

Lung Liver Brain Bone

Question 46

What are the common sites of metastasis for colorectal cancer?

Answer 46

Liver | lung

Question 47

What are the common sites of metastasis for stomach cancer?

Answer 47

Oesophagus Liver Lung

Question 48

What are the common sites of metastasis for lung cancer (non small-cell)?

Answer 48

Adrenal gland Liver Bone Brain

Question 49

What are the common sites of metastasis for pancreatic cancer?

Answer 49

Liver | Lung

Question 50

What are the common sites of metastasis for prostate cancer?

Answer 50

Bone