Tumour Progression, Invasion and Metastasis Flashcards

1
Q

2 characteristics of malignant tumours

A

Progression: unlimited growth (not self-limited like benign) - however needs adequate blood supply to prevent hypoxia

Invasiveness: tumour migrates into surrounding stroma where they then disseminate to distant organs

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2
Q

Describe 4 molecular bases for tumour progression? + causes of each
ACGE

A
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3
Q

Describe what cellular heterogeneity is and how it is related to tumour composition

A

Cellular heterogeneity: the idea that selective pa’s determine tumour composition, which vary in:

  • Antigenicity
  • Growth rate
  • Response to hormones & cytotoxic drugs
  • Capacity for invasion + metastasis
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4
Q

Outline the 4 mechanisms needed for tumour cell invasion

A

Inc. mechanical pa due to rapid cell proliferation
Inc. blood supply
Inc. malignant cell motility (change from epithelial to mesenchymal transition- EMC)
Inc. degradative enzymes by tumour & stromal cells

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5
Q

Why is the concept of hypoxia and angiogenesis important in tumour development?

A

A tumour cant grow beyond 2mm as its size is limited by hypoxia - however this hypoxia will promote Angiogenesis so tumour can continue to grow :)

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6
Q

Describe 4 step mechanism of hypoxia leading to angiogenesis and how this angiogenesis is regulated

A

Hypoxia induces HIF-1 which increases expression of angiogenic factors

Hypoxia also upregulates proteases, degrading the basement membrane

Specialised endothelial cells migrate to tumour, forming new vessels

VEGF stimulates DLL4, which binds to Notch-1 receptors =downregulating VEGF. This + PDGF-b suppresses vessel proliferation

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7
Q

4 key growth factors in angiogenesis?
What are they useful for?

A
  • Vascular Endothelial Growth Factor (VEGF)
  • Fibroblast Growth Factor-2 (FGF-2)
  • Transforming Growth Factor-β (TGF- β)
  • Hepatocyte growth factor/scatter factor (HGF/SF)

Useful for targeted therapies eg Sorafenib targets VEGFA

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8
Q

What is epithelial mesenchymal transition? Why is it related to tumor cell invasion?

A

EMT is the remodelling of cell-cell + cell-ECM interactions - leads to epith cells detaching from each other & the basement membrane

Causes increased metastatic potential, greater resistance + colonisation

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9
Q

How do epithelial cells change in EMT + 3 other things they gain?

A

Goes from:
Epithelial → fibroblast shape/ motility
Cytokeratin → Vimentin filament
E cadherin → N cadherin.

Also gains: invasiveness, mesynchymal genes, protease

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10
Q

How is proteolytic activity of tumours regulated?

A

Proteolysis depends on balance between proteinases & proteinase inhibitors
Most tissues have many TIMPs (Tissue Inhibitor of Metalloproteinases).
Some e.g. pancreatic tumours, have decreased levels of TIMPs

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11
Q

Describe the seed and soil hypothesis to explain how cancer cells metastasise

A

“Plant seeds are carried in all directions but can only live/grow if they fall on congenial soil”.

= therefore only specific adhesions between tumour & endothelial cells in the target organ can create good environments for colonization!

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12
Q

What is a liquid biopsy?
3 advantages + 1 thing it can collect

A

Sampling non-solid tissue, primarily blood.
-Minimally invasive
-Detects molecular biomarkers
-Representative of tissue/s from which it has spread.

Can collect CTC’s

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13
Q

Describe circulating tumour cells + 2 limitations of them

A

Single cells/cell clusters that detached from a tumour + travel through the bloodstream
Marker for tumour growth, prognosis & treatment response

2 Limitations:
BUT they’re v rare (1-10 per 1ml blood) + have short half-life (<2.5h)
So, sensitive/specific methods needed to study them

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14
Q

5 reasons why we use liquid biopsies?

A

Can detect mutations which are v specific to tumour cells
Primary tumour info may not= current cancer status
Molecular properties within tumour + between metastatic sites differ
No need to identify tumour site before biopsy, allows repeated sampling
Used in early detection, or checks for cancer resistance

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