L03: Tumour Biology

Question 1

What is the definition of metastasis

Answer 1

A tumour that deport discontinuous with the primary tumour

Question 2

What must a cell be able to do to for metastasis

Answer 2

1) Detach from primary tumour
2) Invade the extracellular matrix by breaking through the basement membrane
3) adhere to the endothelium within the blood vessels
4) extravasate to secondary sites
50 colonise and survive in the secondary organ

Question 3

How do cells detach from the primary tumour

Answer 3

Adhesion molecules between the cells become downregulated or lost in the cell

Question 4

Name an adhesion molecule that is downregulated in epithelial cancer

Answer 4

E-Cadherin

Question 5

What is the role of e-Cadherin

Answer 5

Adhere 2 cells together

Question 6

What molecule is part of e-Cadherin

Answer 6

Beta catenin

Question 7

If we lose e-Cadherin what can happen to beta-catenin

Answer 7

Become free

Question 8

In a normal cell what happens if beta-catenin becomes free and is no longer part of e-Catherine

Answer 8

A complex that involved APC degrades it

Question 9

What is APC

Answer 9

Tumour supressor gene

Question 10

Why is free beta catenin dangerous

Answer 10

Floating b catenin can cause it to bind to transcription factors and promote oncogenes transcription

Question 11

Which oncogenes can become transcribed

Answer 11

MYC

Question 12

What does MYC or oncogenes lead to

Answer 12

Uncontrolled proliferation

Question 13

If in a tumour we have loss of e-Cadherin and loss of APC that degrades beta-catenin what can happen

Answer 13

Beta catenin will become freely available to drive oncogenes

Question 14

Overall what does the loss of e-cadherin and loss of apc show

Answer 14

Knock on effects to the loss of e-Cadherin

Question 15

After the loss of adhesion what happens to the tumour for it to metastasis

Answer 15

Invade the surrounding connective tissue

Question 16

What allows the the breakage of basement membrane to have the cell filter to the stroma

Answer 16

Degrading enzymes

Question 17

What are the degrading enzymes known as

Answer 17

Matrix metalioproteinases (MMPs)

Question 18

What are MMPs secreted by

Answer 18

Tumour cells
Or
Stroma

Question 19

What causes the stroma to release MMP’s

Answer 19

Soluble factors produced by pre-malignant dysplastic epithelium

Question 20

What specific feature within the stroma produces MMPs

Answer 20

Activated fibroblasts

Question 21

What is epithelial mesenchyme transition

Answer 21

A normal process that is seen in wound healing where epithelial cells are damaged and remaining epithelial cells form to mesenchymal cells to proliferate

Question 22

What happens to the mesenchymal cells that proliferate in EMT

Answer 22

Reverse back to epithelial morphology

Question 23

In cancer what happens to the EMT process

Answer 23

Cancer called hijack EMT and enable cancer cells to migrate through the extracellular environment

Question 24

After the cancer has invaded the stroma what happens next

Answer 24

Intravasation through leaky cell junctions

Question 25

What happens when the cell has invaded the vasculature

Answer 25

The cells enter smaller capillaries as they flow in the blood and slow down by size restriction

Question 26

When cells slow down by size restriction what happens to the cell so it become extravated to the secondary site

Answer 26

Adhere to the endothelium through receptor ligand interactions

Question 27

Is cancer spread to specific sites random

Answer 27

No

Question 28

Why is the cancer spread not random

Answer 28

Due to the seed and soil hypothesis

Question 29

What is the seed and soil hypothesis

Answer 29

Metastatic tumours metastasize where the micro-environment is favourable just like a seed will only grow if it lands on fertile soil

Question 30

Do all circulating tumours give rise to metastatic disease

Answer 30

No because it can become detected and destroyed by the immune system

Question 31

What allows the secondary site to be favourable for a cancer cell

Answer 31

Metastatic niche

Question 32

What is a metastatic niche

Answer 32

When the primary tumour cells secrete factors that act on secondary sites to modify the environment and recruiting host immune cells so the cancer cells can proliferate there later on

Question 33

What type of condition does a tumour usually have

Answer 33

Hypoxia

Question 34

Which specific region of the tumour is hypoxic

Answer 34

Inside of the tumour i.e necrotic tumour

Question 35

If tumour cells are hypoxic how do they respond

Answer 35

By initiating angiogenesis

Question 36

What is angiogenesis

Answer 36

New formation of blood vessels

Question 37

Which transcription factor controls angiogenesis

Answer 37

HIF

Question 38

What does angiogenesis allow

Answer 38

Supplies oxygen and nutrients to the necrotic tumour and takes away its waste Increases survival

Question 39

Apart from angiogenesis what does the hypoxic response also do

Answer 39

Switch from areobic to anaerobic respiration

Question 40

If anaerobic respiration is occuring where does most of the energy come from

Answer 40

Glycolysis

Question 41

What does glycolysis involve

Answer 41

Upregulating glucose

Question 42

How can we visualise tumours using the knowledge on glycolic switch

Answer 42

1) Give a patient glucose analogue called flurodeoxyglucose | 2) screen with a PET scan

Question 43

What does glycosis of tumour cells enable

Answer 43

Compete with normal cells for scarce glucose supply

Question 44

If cancer cells compete for glucose with normal cells, what happens to normal cells

Answer 44

Cell death

Question 45

What by-product is produced as a result of anaerobic respiration

Answer 45

Lactic acid

Question 46

What can lactic acid do to the environment that leads to further death of normal cells

Answer 46

Acidify it