Tumour Progression and Metastasis

Question 1

Metastasis can be ___ but never really ___

Answer 1

Metastasis can be managed but never really cured.

Question 2

How many changes are needed for metastasis?

Answer 2

A lot, because a cell needs to be able to move, and then grow where it shouldn’t be

Question 3

80% of breast cancers metastasise to bone, why is that?

Answer 3

Because they tend to have a master regulator of bone development that is normally only found in bone, expressed in breast

Question 4

What’s the biggest risk factor for cancer?

Answer 4

age

Question 5

Why is age the biggest risk factor for cancer?

Answer 5

Lost the capcacity to repair DNA.
Have accumulated mutations.
Reduced immune surveillance

Question 6

Explain the stepwise model of mutations leading to metastasis

Answer 6

Sequential mutations that accumulate. Removing a negative cell cycle regulator, activating a positive regulator, inhibiting cell death, all leading to transformation

Question 7

Tumour cells affect the environment and…

Answer 7

Create a tumour microenvironment, and the environment made then affects the cells.

Question 8

If you completely remove a tumour, why can that not be enough to cure?

Answer 8

Cells may have metastasised and then be dormant. Can be reactivate through any number of things

Question 9

What transition does a cell need to go under to metastasise?

Answer 9

Epithelial to mesenchymal transition, and then back again

Question 10

Name the steps in carcinoma progression

Answer 10

Hyperplasia, carcinoma, invasive carcinoma, metastatic carcinoma

Question 11

Name some of the hallmarks of cancer

Answer 11

Genome instability, resist cell death, avoid immune destruction, access vasculature, evade growth supressors, sustained proliferative signalling, phenotypic plasticity, deregulated metabolism

Question 12

What is Transcolemic spread?

Answer 12

Where a cancer penetrates the peritoneum cavity, e.g. ovary -> liver

Question 13

What is haematogenous spread?

Answer 13

Cancer enters blood vessels, can reach many distant locations

Question 14

What is lymphatic spread?

Answer 14

Cancer goes to lymph nodes. Lymphatic system is large network that drains much of the body. Can lead to Haematogenous spread.

Question 15

What is the seed and soil theory?

Answer 15

Cancer cells die easily in the wrong environment. They need a good, similar location to land in.

Question 16

What does the theory contrary to the seed and soil theory say?

Answer 16

That cells land where they naturally drain to.

Question 17

What are the early events of metastasis?

Answer 17

Loss of tissue organisation, cells lose some identity, detach from where they are and then breach the basement membrane.

Question 18

Once a cancer cell has breach the basement membrane, what else do they need to cross?

Answer 18

The stroma and endothelial layer

Question 19

How do adhesion changes promote the movement of cancer cells?

Answer 19

Ability to invade the stroma and endothelial lining. Can survive in inappropriate contexts. Can enter circulation.

Question 20

What was James Ewing’s big idea?

Answer 20

Circulation predicting the site of metastasis. Cells travel in clumps and often get entrapped in the first vascular bed they come across.

Question 21

Cells typically have a top and bottom, this is called? certain cell types have it disrupted in cancer causing?

Answer 21

Polarisation.
Basal cell carcinoma, squamous cell carcinomas. If any more disruption, would become invasive.

Question 22

How do cells stay in their normal place? What adhesion is there?

Answer 22

Cell-Cell adhesion - E-cadherin and desmoplakin.Desmosomes are intermediate filament.
Gap junctions.

Cell-ECM adhesion. - Integrins, Laminin (hemidesmosome), focal adhesions

Question 23

In an EMT, what happens to E-cadherin?

Answer 23

Replaced by N-cadherin.
Lost by TFs, degradation, phosphorylation, methylation of gene etc.

Question 24

How can cells sometimes file down a path into the blood?

Answer 24

If a cell gets the ability to make collagenases it will carve out a path.

Question 25

When using antibodies to track EMT, what proteins can you look at?

Answer 25

E-cadherin for Epithelial
N-cadherin for mesenchyme

Question 26

What are some key TFs that cause EMT to take place by regulation E-cadherin and some signalling?

Answer 26

Snail, Twist and ZEB

Question 27

What do circulating tumour cells tend to clump with?

Answer 27

Immune cells and platelets which affect their properties.

Question 28

Cancers tend to be more agressive if more of their circulating tumour cells are….?

Answer 28

Mesenchymal

Question 29

What does CXCR4 do in breast cancer

Answer 29

It’s a receptor for certain cytokine that helps breast cancer cells to home in on certain sites