Brainscape's Knowledge GenomeTM

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


See full index

Molecular Basis Of Disease > Tumour Angiogenesis, Invasion & Metastasis > Flashcards

Tumour Angiogenesis, Invasion & Metastasis Flashcards

1
Q

State the 3 major 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

Describe the 3 major characteristics of malignant tumours

A
  • Growth: Unlimited (not self-limited like benign T) - only if there is adequate blood supply
  • Invasive: Migration of tumour cells into surrounding stroma - free to disseminate via vascular or lymphatic channels to distant organs
  • Metastasis: Spread of tumour cells from the primary site - secondary tumours formed at other sites in the body
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

State the 4 key steps involved in cancer progression?

A
  • Transformation: extensive mutagenic + epigenetic changes followed by clonal selection
  • Angiogenesis: new blood vessel formation
  • Motility and invasion: Epithelial to mesenchymal transition, invasive properties allowing intravation into circulation and extravation from circulation to tissues
  • Metastasis: Colonisation of target organs, gives ability to expand from micrometastases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Define angiogenesis

A

Formation of new blood vessels from pre- existing vessels

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

Define vasculogenesis

A

Formation of new blood vessels from progenitors

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

State the 3 types of angiogenesis and their function?

A
  • Developmental vasculogesis: Organ growth
  • Normal Angiogenesis: wound repair, placenta during pregnancy, cycling ovary
  • Pathological Angiogenesis: Tumour A ocular (eye) + inflammatory disorder
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe the neovascularization of tumours?

A
  • Natural formation of new blood vessels
  • Infiltrate into tumour tissue
  • Tumours won’t grow beyond a size of 1-2 mm3 without own blood supply
  • So for context - There are three different pathways that comprise neovascularization: (1) vasculogenesis, (2) angiogenesis, and (3) arteriogenesis. [2]
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe the process behind tumour angiogenesis?

A
  • Small tumour grows to 1-2mm^3 when delivery of oxygen + nutrients from nearby capillaries becomes limiting (hypoxia) -> Tumour switches on expression of angiogenic genes/factors that initiate new blood vessel growth -> New network of blood vessels grows in + around the tumour (TA) -> the delivery of oxygen + nutrients -> increase growth + provides a route for cells to shed off & spread
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe features of tumour hypoxia and what it activates?

A
  • Low 02 tension < 1% -> Strong stimulus for tumour angiogenesis -> Increase distance from capillaries -> increase in Tumour hypoxia
  • Activates transcription of genes involved in angiogenesis, tumour cell migration + metastasis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

State what 4 Angiogenesis genes can be activated from tumour hypoxia?** check over

A
  • Vascular endothelial growth factor
  • Glucose transporter 1
  • Urokinase plasminogen activator receptor
  • Plasminogen activator inhibitor 1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

State angiogenic factors that have a role aside from forming new blood vessels and describe how these factors are secreted?

A
  • stimulate the directional growth of endothelial cells
  • Vascular Endothelial Growth Factor, Fibroblast Growth Factor 2, Placental growth factor + Angiopoietin 2
  • Factors are secreted by tumour cells or stored bound to components of the extracellular matrix + released via Matrix metalloproteinase 2 enzyme
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe the Vascular endothelial growth factor (VEG) signalling pathway?

A
  • VEGF binds to VEGF-R2 on endothelial cells
  • VEGF/VEGF-R2 dimerizes at the plasma membrane + recruits cofactors
  • Activate 3 major signal transduction pathways - cell survival, vascular permeability, gene expression + cell proliferation
  • Required for angiogenesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe the 3 functions of mechanisms of tumour cell motility and invasion?

A
  • Mechanical pressure caused by rapid cellular proliferation
  • Motility of the malignant cells (epithelial to mesenchymal transition)
  • Production of degradative enzymes by both tumour cells and stromal cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe the epithelial-mesenchymal transition mechanism?

A
  • Transition of polarised epithelial cells via upregulaiton of marker genes to mesenchymal cells
  • Epithelial P -> Loss of -> Epithelial shape and cell polarity (3-catenin, claudin-1), Cytokeratin intermediate filament expression + Epithelial adherens junction protein (E-cadherin) -> Acquisition of -> Fibroblast-like shape and motility, Invasiveness (gaps formed), Vimentin intermediate filament expression, Mesenchymal gene expression (fibronectin, PDGF receptor, avß6 integrin) + Protease secretion (MMP-2, MMP-9) -> M phenotype
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe the role of E-cadherins in epithelial cells?

A
  • Epithelial marker
  • Homotypic adhesion molecule (adhesion of cells with the same cadherin)
  • Calcium-dependent
  • Inhibits invasiveness + Binds B-catenin
  • Allows for cell-cell adhesion (^ density) + contact inhibition (monoloayer of cells formed)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe the contribution of stromal cells in tumour progression

A

Factors released by stromal cells (macrophages, mast cells, fibroblasts) include angiogenic factors, growth factors, cytokines, proteases

17
Q

Describe the contribution of stromal cells in tumour progression and describe an example involved?

A

Urokinase-type plasminogen activator
- Activated by tumour cells
- Causes plasmin production
- Plasmin activates matrix metalloproteinases (MMPs)
- Allows invasion by degrading extracellular matrix (ECM) + releasing matrix- bound angiogenic factors such as transforming growth factor-B1.

18
Q

Describe the steps involved in cancer dissemination from the point of primary tumour formation

A
  • Primary tumour formation -> localized invasion -> Intravasation -> transport through circulation -> arrests in microvessels of various organs - extravasation -> formation of micrometastasis -› colonization (macrometastasis formation)
19
Q

Describe the efficiency of the process?

A
  • The overall process is highly inefficient:
  • Tumour cells can extravasate successfully (>80%) but the last two steps are very inefficient <0.02% of cells actually form micrometastases).
20
Q

Describe 1 hypothesis that determine the pattern of tumour spread?

A
  • Mechanical Hypothesis -> Anatomical considerations -> Blood and lymphatic systems, entrapment in capillary beds (20-30mm carcinoma cell, 8 Um capillary) + organs close by
21
Q

Describe the other hypothesis that determine the pattern of tumour spread?

A
  • Seed and Soil Hypothesis -> Specific adhesions between tumour cells and endothelial cells in the target organ, creating a favourable environment in the target organ for colonisation -> Genetic alterations acquired during progression allow tumour cells to metastasize
22
Q

What components of tumour angiogenesis, motility + invasion can be targeted to inhibit cancer and describe them?

A
  • Only Tumour angiogenesis
  • Success with targeted therapy to angiogenic factors like vascular endothelial growth factor
23
Q

Name an anti-angiogenesis drug and its mechanism of action?

A
  • Avastin
  • monoclonal AB -> Binds VEGF -> prevents VEG binding to
    VEG receptors on endothelial cells

Molecular Basis Of Disease (30 decks)

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