Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MBD > Tumour Angiogenesis, Invasion And Metastasis > Flashcards

Tumour Angiogenesis, Invasion And Metastasis Flashcards

1
Q

What are the characteristics of malignant tumours?

A
  • Growth
  • Invasiveness
  • Metastasis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the growth potential of a malignant tumour?

A

Unlimited as long as adequate blood supply is available

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is a malignant tumour? How does it differ to a benign cancer?

A

Malignant tumour has unlimited growth potential

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the invasiveness characteristic of a malignant tumour?

A

Migration of tumour cells into the surrounding stroma (ECM) where they are free to disseminate via the circulatory or lymphatic system to metastasise

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the metastatic characteristic of a malignant tumour?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the key steps in cancer progression?

A
  1. Transformation
  2. Angiogenesis
  3. Motility and invasion
  4. Metastasis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is transformation of a cancer?

A

Extensive mutagenic and epigenetic changes followed by clonal selection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Define exactly what angiogenesis is

A

Formation of new blood vessels from pre-existing capillaries

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Why do tumours undergo angiogenesis?

A

As it grows it will be limited by hypoxia - angiogenesis overcomes this

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is vasculogenesis?

A

This is the formation of a primitive vascular network (so new blood vessels) from progenitor cells, so can be thought of as a step before angiogenesis

  • usually only in organ growth during development
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the types of angiogenesis?

A
  • Developmental (vasculogenesis)
  • Normal angiogenesis
  • Pathological angiogenesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is pathological angiogenesis?

A
  • Tumour angiogenesis
  • Seen in ocular and inflammatory disorders
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

When does normal angiogenesis occur?

A
  • Wound repair
  • Placenta during pregnancy
  • Cycling ovary
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Roughly how big (mm3) does a tumour not grow further than without its own blood supply?

A

1-2mm3 without their own organ blood supply

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What type of molecules are angiogenic factors - describe their properties?

A
  • Cytokines and proteins
  • Are growth factors that allow for vascular endothelial cell growth and are also chemotactic (meaning that cells grow towards them)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is meant by the angiogenic switch of the tumour?

A

This is where a stimulus causes an upregulation of angiogenic factor and their secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the steps in tumour angiogenesis?

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Name the stimulus that causes the turning on of the angiogenic switch (what is it that causes a tumour to suddenly express angiogenic factors?)

A
  • Hypoxia! (below 1% oxygen tension)
  • Increases with growing distance from the capillaries.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Explain how this stimulus causes angiogenesis

A

Hypoxia in the cells farthest away from the blood supply will cause activation of transcription of genes involved in angiogenesis, cell migration and metastasis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What 4 genes are involved in angiogenesis?

A
  • VEGF: Vascular endothelial growth (most important)
  • GLUT-1: Glucose transporter 1
  • u-PAR: Urokinase plasminogen activator receptor
  • PAI-1: Plasminogen activator inhibitor 1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Why is the one of these genes upregulated by a glucose transporter?

A

As hypoxic cells need a high glucose uptake to sustain themselves by non-oxidative phosphorylation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What does plasminogen activator 1 cause?

A

Invasion and metastasis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

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

A
  • Vascular endothelial growth factor (VEGF)
  • Fibroblast growth factor 2 (FGF2)
  • Placental growth factor (PIGF)
  • Angiopoetin 2 (Ang2)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the role of matrix metalloproteases in this mechanism of angiogenesis?

A

Angiogenic factors are secreted by tumour cells or are stored bound to components of the ECM and may be released by matrix metalloproteases

  • MMPs have a role in allowing for invasion of blood vessels into the ECM
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the angiogenic factors secreted by?

A

Tumour cells or components of the extracellular matrix

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What receptor does VEGF bind to on endothelial cells, what type of receptor is it?

A

VEGF-R2 (one of a few in a family)

  • Tyrosine kinase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Explain what happens when VEGF binds to its receptor here

A

VEGF-R2 dimerises at the membrane and recruits cofactors that subsequently activate 3 major signal transduction pathways

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Name the 3 major signal transduction pathways that this binding of VEGF uses

A
  • Phospholipase gamma!
  • Protein kinase B
  • Ras
29
Q

Describe what the 3 pathways (binding of VEGF uses) achieve for the endothelial cell which ultimately lead to angiogenesis

A
  • Cell survival
  • Vascular permeability
  • Gene expression
  • Cell proliferation
30
Q

Which of the signalling pathways is especially important in promoting cell survival?

A

Protein kinase B

31
Q

Explain what is meant by the epithelial-mesenchymal transition of the malignant cells

A

This is a phenotypic switch where the cells lose the epithelial shape and properties and become a fibroblast-like cell

32
Q

Describe the properties of the cells that are lost in this switch? Also name some epithelial markers that are lost

A

Loss of:

  • epithelial shape and polarity
  • Cytokeratin intermediate filament expression
  • Epithelial adherens junction position
33
Q

Describe the properties of what the cells become in this switch and some mesenchymal cell markers

A

Become fibroblast like in terms of shape and motility

  • increased invasiveness
  • express vimentin intermediate filaments
  • protease secretion (MMP2 and MMP9)
  • other mesenchymal gene expression (fibronectin, PDGF receptor …)
34
Q

Describe the differences in shape of these two cells (endothelial cells vs fibroblasts)in culture

A

Endothelial cells form a nice monolayer of closely associated cells but fibroblasts are long cells that are very motile

35
Q

What proteases are secreted in the epithelial-mesenchymal transition?

A

MMP-2 and MMP-9

36
Q

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

A

Beta-catenin and cloudin-1

37
Q

What is the function of E-Cadherins?

A

Adhesion of epithelial cells with the same cadherin - loss of E-cadherin or loss of function causes cells to grow on top of each other instead of in a monolayer

  • allow for maintenance of normal epithelial cell polarity
38
Q

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

A

E-cadherin

39
Q

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

A

Fibronectin, PDGF receptor, alpha 5 beta 6 integrin

40
Q

What are E-cadherins?

A

Homotypic adhesion molecules

41
Q

What are E-cadherins dependant on?

A

Calcium

42
Q

What do E-cadherins inhibit?

A

Invasiveness

43
Q

What does E-cadherin bind to?

A

Beta-katenin

44
Q

What is meant by epithelial cell contact inhibition?

A
  • Once epithelial cells are in contact with other epithelial cells with the use of cell-cell adhesion molecules such as E-cadherin, they inhibit migration and proliferation of each other.
  • So at low density, the cells proliferate until higher density when they inhibit proliferation and motility.
45
Q

If there is loss of E-cadherin in a cancerous cell (from E-M transition) the cell becomes mote motile but what is released by the cell to increase invasiveness?

A

Release of enzymes like matrix metalloproteases

46
Q

What forms a tumour mass?

A

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

47
Q

What factors are released by stromal cells?

A

Angiogenic factors, growth factors, cytokines and proteases

48
Q

Give an example of a molecule released by stromal cells in this process

A

uPA - urokinase type plasminogen activator

49
Q

Explain the effect of this molecule (uPA) on cancer cells

A
  • uPA will bind to receptor on cancer cells and will result in plasmin production FROM PLASMINOGEN
  • uPA is not to be confused with tissue plasminogen activator in the blood system
50
Q

What does plasmin activate?

A

Matrix metalloproteases

51
Q

What do matrix metalloproteases do?

A
  • Degrade extracellular matrix
  • → Release matrix-bound angiogenic factors

→ increased invasiveness

52
Q

What is an example of a matrix bound angiogenic factor?

A

Transforming growth factor-beta1

53
Q

Describe the efficiency of the various steps in cancer metastasis

A
  • The first step of cancer cells moving into the blood is around 80% efficient
  • But the last two steps (formation of a micrometastasis and a macrometastasis) is very inefficient (less than 0.02%)
54
Q

What are the hypotheses for pattern of tumour spread?

A
  • Mechanical hypothesis
  • Seed and soil hypothesis
  • Genetic alterations acquired during disease progression
55
Q

Describe the mechanical hypothesis for why specific cancer sites metastasise in specific organs more regularly than expected

A

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

56
Q

Describe the seed and soil hypothesis for why specific cancer sites metastasise in specific organs more regularly than expected

A

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

57
Q

What tumour processes can be targeted to inhibit cancer?

A
  • Tumour angiogenesis
  • Cell motility
  • Invasion
58
Q

Have we had any success in targeting cell motility (cell-cell adhesion molecules)?

What about invasion (matrix metalloproteases)?

A

No to both

59
Q

Explain the angiogenesis hypothesis

A

If we were to be able to keep a tumour indefinitely in the non-vascularised, dormant state, then it is possible that we can keep it from metastasising

  • both the tumour and the microvascular compartment are valid therapeutic targets
60
Q

Name an example of a cancer that is highly angiogenic

A
  • Kidney cancer (renal cell carcinoma)
  • This helped us to understand the biology of how VEGF is involved in driving angiogenesis and was successfully treated to inhibit angiogenesis
61
Q

What is avastin?

A

Monoclonal antibody drug that targets anti-angiogenesis

62
Q

What types of cancer is avastin approved for?

A
  • Colorectal, lung, kidney, ovarian
63
Q

How does avastin work?

A
  • Binds to VEGF and prevents it from binding to VEGF receptors on endothelial cells
  • not a cure but reduces tumour burden
64
Q

What are the common sites of metastasis for breast cancer?

A
  • Lung
  • Liver
  • Brain
  • Bone
65
Q

What are the common sites of metastasis for colorectal cancer?

A
  • Liver
  • lung
66
Q

What are the common sites of metastasis for stomach cancer?

A
  • Oesophagus
  • Liver
  • Lung
67
Q

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

A
  • Adrenal gland
  • Liver
  • Bone
  • Brain
68
Q

What are the common sites of metastasis for pancreatic cancer?

A
  • Liver
  • Lung
69
Q

What are the common sites of metastasis for prostate cancer?

A

Bone

MBD (23 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions