Intro To Metastasis Flashcards

1
Q

Difference between malignant and benign neoplasms

A

Benign - well differentiated, non invasive, genomically stable, encapsulated, low mitotic rate
Malignant- undifferentiated, invasive, genomically unstable, non ecapsulated, high division rate

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2
Q

Define metastasis

A

When a tumour cell leaves the primary tumour, travels to a distant site and establishes a secondary tumour

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3
Q

Why is metastasis common?

A

Millions of tumour cells shed daily into circulation, depending on tumour
Metastatic cells can have dormant phase

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4
Q

Describe the metastasis process

A

Tumour cell breaks off primary tumour and enters ECM
MMPs secreted to degrade ECM and allow movement through BM and into vasculature
EMT signals facilitate motility and intravasation
Cells travel in blood vessels- survival and dormancy at distant sites
Tumour cells enter tissues through junctions due to weak adhesion of tumour cells to endothelial cells
Open pathway created for other tumour cells
Colonisation of new tissue

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5
Q

MMP function in normal cells

A

MMPs cleave portion of ECM
Modify interaction between cellular adhesion molecules and ECM components
ECM cleavage used to free up space, modify signalling molecules

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6
Q

What molecule of ECM is especially disregulated in metastasis?

A

E cadherin
Anchors cell to surrounding cells and stabilises cytoskeleton.
In cancer cells cleavage of e cadherin by MMPs is increased = cells are free to move

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7
Q

What are lytic enzymes and how are they classified?

A
Enzymes which break down ECM
Can be:
Serine-
Cysteine-
Aspartyl- proteases
Or MMPs
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8
Q

Serine proteases in ECM degradation

A

Plasmin
Plasminogen activators
Cathepsin G

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9
Q

What is plasmin

A

Protease that degrades fibronectin and laminin

Involved in angiogenesis

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10
Q

Plasminogen activators

A

What Urokinase plasminogen activator (uPA) is bound to surface of tumour cells
Following plasminogen activation there is tissue invasion
PA inhibitor proteins (PAI1/2) are upregulated in metastatic cancer
Inhibitors could be used as anticancer agents

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11
Q

Influence of integrins in metastasis

A

Affect MMP activity

MMPs need to be activated by integrins

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12
Q

Change of cadherin expression in cancer

A

Switch from e cadherin to n-cadherin ( more embryonic)
This is epithelial mesenchymal transition
This switch leads to increased tumour cell invasion

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13
Q

4 factors determining destination sites for metastatic tumours

A

Venous drainage blood flow - blood supply
Chemotaxis- the organ produces factors that attract tumour cells
Compatible adhesion sites on endothelial surface
Appropriate GFs and ECM environment

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14
Q

Contribution of inflammation to metastasis

A

Tumour cell expression of chemokine receptors
Chemokines induce directed chemotaxis in nearby responsive cells
Chemokines normally regulate leukocyte recirculation and trafficking to sites of inflammation
Allow tumour cells to reach sites of metastasis

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