Tumour Biology Flashcards

1
Q

Define metastasis.

A

A tumour deposit that is discontinuous with the primary tumour.

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2
Q

List the processes involved in the metastatic cascade.

A

1 - Detachment from primary tumour and invasion of extracellular matrix.

2 - Intravasation.

3 - Migration.

4 - Extravasation.

5 - Colonisation.

*The rest of the lecture goes through each of these points in order.

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3
Q

What is the rate limiting step in metastasis?

Why might this be?

A
  • Colonisation.
  • This is because most metastatic cells die after extravasating because they are unlikely to be adapted to the new environment.
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4
Q

What facilitates detachment of metastatic cells from the primary tumour?

A

Downregulation of adhesion molecules such as E-cadherin.

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5
Q

In which cells are E-cadherins most common?

A

Epithelial cells.

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6
Q

How does E-cadherin work?

A
  • Two E-cadherin molecules on cell surfaces bind to a cell’s actin filament by binding to beta catenin on the actin filaments.
  • E-cadherin molecules on other cell surfaces bind to other E-cadherin molecules, linking the actin filaments.
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7
Q

What happens to beta catenin if E-cadherin is not present to bind to it?

Why is this important?

A
  • It becomes free in the cytoplasm, triggering a failsafe response which clears beta catenin from the cell by way of the ubiquitin-proteasome system.
  • This is important because free beta catenin is carcinogenic.
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8
Q

What is APC?

A

A tumour suppressor gene which acts as a negative regulator of beta catenin.

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9
Q

List 2 biological processes that are particularly common in the formation of colorectal cancer.

What is the common effect of these biological processes?

A

1 - E-cadherin is downregulated.

2 - APC is deleted, leading to the loss of its expression.

  • These processes cause an increase in free beta catenin.
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10
Q

How does free beta catenin increase risk of developing cancer?

A

It is able to translocate to the nucleus, where it is able to interact with transcription factors to drive the expression of genes that promote cell proliferation such as MYC.

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11
Q

What are matrix metalloproteinases (MMPs)?

A
  • Enzymes that are normally involved in tissue remodelling as part of wound healing.
  • In the stroma surrounding cancer cells, these enzymes are often increased in expression.
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12
Q

How are matrix metalloproteinases involved in metastasis?

A
  • The developing cancer cells produce soluble factors that diffuse through the basement membrane.
  • These factors activate the cells of the stroma.
  • This increases production of matrix metalloproteinases.
  • Matrix metalloproteinases allow the cancer to invade the basement membrane.
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13
Q

How do benign tumours feel different from malignant tumours on palpation?

Why might this be?

A
  • Benign tumours feel soft.
  • Malignant tumours feel hard.
  • This is because malignant tumour tissue contains many collagen-producing fibroblasts which secrete matrix metalloproteinases.
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14
Q

Define dysplasia.

A

The presence of cells of an abnormal type within a tissue, which may signify a stage preceding the development of cancer.

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15
Q

When do epithelial cells need to migrate?

How do epithelial cells migrate?

A
  • During wound healing.

- They migrate by a process known as epithelial-mesenchyme transition.

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16
Q

Briefly describe the process of epithelial-mesenchyme transition.

What is the clinical importance of this process?

A
  • Epithelial cells adopt a mesenchymal phenotype.
  • This phenotype allows the cells to migrate.
  • Once migration has completed, the reverse process occurs (mesenchyme-epithelial transition).
  • This is a potential target for cancer invasion (and therefore metastasis).
17
Q

Which transcription factors regulate epithelial-mesenchyme transition?

A

SLUG and SNAIL.

18
Q

Briefly describe the process of tumour extravasation.

A
  • As tumour cells enter small capillaries, they slow due to size restriction.
  • They then adhere through receptor-ligand interactions in a process similar to neutrophil extravasation.
19
Q

What is the seed and soil hypothesis?

A

A hypothesis to explain the non-random pattern of metastasis that says that the ability of a metastatic cancer cell to survive at a distant site is due to the characteristics of both the cancer cell and the environment that it invades.

20
Q

What is James Ewing’s opposing hypothesis to the seed and soil hypothesis?

Which hypothesis is correct?

A
  • That metastasis occurs purely by anatomical and mechanical routes.
  • Both theories are thought to be correct.
21
Q

Define metastatic niche.

A

The process of conditioning an environment to be conducive to metastasis by soluble factors that have been released systemically by the primary tumour.

22
Q

What are the advantages of glycolytic switch in cancers that are normoxic?

A
  • Cancer cells become efficient users of glycolysis as they upregulate:

1 - Cell surface glucose transporters.

2 - Enzymes that metabolise glucose.

  • Upregulation of glycolysis also enables tumour cells to outcompete normal cells for scarce glucose supply.
  • This is made further by the relative resistance of cancer cells to a low of pH caused by an increase in lactate production.
23
Q

How are PET scans used to produce images of cancer?

A

PET uses a glucose analogue known as fluorodeoxyglucose, which, similar to glucose, is rapidly taken up by cancer cells.

24
Q

How is angiogenesis in cancerous tissue specialised to facilitate invasion and metastasis?

A
  • Angiogenesis in cancerous tissue produces abnormal blood vessels that are abnormally porous.
  • This facilitates migration of metastatic cells out of the circulation.
25
Q

Define anoikis.

A

Detachment-induced cell death.

26
Q

List 2 molecules secreted by tumours that contribute to the formation of pre-metastatic niches.

What is the name of the phase in which these molecules are secreted?

A

1 - Tumour-derived secreted factors.

2 - Extracellular vesicles.

  • The priming phase.
27
Q

Which organ is involved in reinforcing pre-metastatic niches?

How does it do this?

What is the name of the phase in which these molecules are secreted?

A
  • The bone marrow.
  • By secreting cytokines.
  • The licensing phase.
28
Q

What is the role of macrophages in tumour metastasis?

A
  • Tumours recruit macrophages by CSF-1.
  • Macrophages secrete epidermal growth factor, for which tumours have many receptors.
  • This promotes growth.
29
Q

What is an invadopodia?

What is its function?

A
  • A structure at the apical surface of a cell that is highly enriched with proteolytic enzymes and integrin adhesion receptors.
  • Its function is to facilitate invasion.
30
Q

What is intussusceptive angiogenesis?

A

A rapid form of angiogenesis characteristic of tumours that increases the volume of the endothelial cells that already exists (rather than increasing the number of endothelial cells).

31
Q

What is vasculogenic mimicry?

A

A form of angiogenesis where the tumour cells align in a similar fashion to endothelial cells to extend a blood vessel.

32
Q

What is vessel co-option?

A

A non-angiogenic process through which tumour cells utilize pre-existing tissue blood vessels to support tumour growth.

33
Q

List 2 factors that are necessary to maintain a blood supply and avoid vessel destruction.

A

1 - VEGF.

2 - Angiopoietin 2.

*Both of these factors are needed simultaneously.

34
Q

List the stages involved in tumour angiogenesis.

A

1 - Angiopoietin 2 leads to tumour regression.

2 - The tumour becomes hypoxic.

3 - THe tumour upregulates VEGF and angiopoietin 2.

4 - Sprouting angiogenesis occurs.