CELLULAR BIOLOGY - Causes and Hallmarks of Neoplasia

Question 1

What is the most prevalent cause of cancer?

Answer 1

Genomic DNA damage leading to genomic instability and mutation accumulations

Question 2

What are the two main types of DNA damage?

Answer 2

Blockage of replication machinery
Alteration of DNA sequences

Question 3

What endogenous factors can induce mutations within the genome?

Answer 3

Replication errors
Reactive oxygen species

Question 4

What exogenous factors can induce mutations within the genome?

Answer 4

UV radiation
Other types of radiation
Mutagenic chemicals
Chemotherapy
Radiotherapy

Question 5

What is the most common virus that has been proven to induce cancer in animals?

Answer 5

Bovine papillomavirus

Question 6

What is meant by the multi-hit model of cancer development?

Answer 6

The multi-hit model of cancer development refers to the combination of multiple genomic mutations required for cells to become neoplastic. Cells with a mutation become genetically unstable and thus are more susceptible to acquiring more mutations, leading to a mutation accumulation and neoplasia

Question 7

Why does the risk of cancer development increase with age?

Answer 7

The risks of neoplasia increase with age as neoplastic cell development requires mutation accumulations which occur over time, thus making older animals more susceptible to cancer

Question 8

What is a tumour suppressor?

Answer 8

A tumour suppressor inhibits the cell cycle, blocking proliferation and preventing tumour formation

Question 9

Give two examples of tumour suppressors

Answer 9

p53
Retinoblastoma (pRB)

Question 10

Describe what happens to the cell cycle when there is a mutation in the p53 gene?

Answer 10

If the p53 gene has a mutation, cells are unable to trigger cell cycle arrest or apoptosis in response to DNA damage. This allows the mutated cell to continue through the cell cycle with the mutation being copied to the daughter cells leading to genomic instability and the acquisition of more mutations

Question 11

Describe what happens to the cell cycle when there is a mutation in the pRB gene?

Answer 11

If the pRB gene has a mutation, pRB remains in the stimulatory (phosphorylated) state, signalling the mutated cell to continue into the S phase of the cell cycle leading to the mutation being copied to the daughter cells leading to genomic instability and the acquisition of more mutations

Question 12

What are proto-oncogenes?

Answer 12

Proto-oncogenes are normal cells involved in the regulation of cell growth

Question 13

What are oncogenes?

Answer 13

Oncogenes are mutated proto-oncogenes which promote cell proliferation and have the ability to cause cancer

Question 14

What are the three mechanisms of oncogene activation?

Answer 14

Translocation
Gene amplifications
Point mutations

Question 15

What is translocation of oncogenes?

Answer 15

Translocation of oncogenes is a genetic change in which a piece of one chromosome breaks off and attaches to another chromosome and is now under the control of a strong promoter

Question 16

What is gene amplification in terms of oncogene activation?

Answer 16

Gene amplification increases the number of oncogene copies through repeated duplication of the oncogenes resulting in increased protein levels

Question 17

What are point mutations in terms of oncogene activation?

Answer 17

Point mutations are the expression of the oncogenes with an enhanced function

Question 18

What are the six hallmarks of cancer?

Answer 18

1. Self-sufficiency in growth factors
2. Insensitivity to ‘anti-growth’ signals
3. Evasion of apoptosis
4. Limitless replicative potential
5. Sustained angiogenesis
6. Tissue invasion and metastasis

Question 19

Healthy cells require a positive growth signal in order to replicate, however, neoplastic cells can replicate with or without growth factors present. List the three mechanisms neoplastic cells use to achieve this

Answer 19

• Neoplastic cells can synthesise their own growth factors
• Neoplastic cells can syntheses more growth receptors
• Neoplastic cells can bypass the need to growth factors or growth receptors through modifying intracellular pathways

Question 20

How can neoplastic cells achieve insensitivity to ‘anti-growth’ signals?

Answer 20

Neoplastic cells mutate tumour suppressor genes such as p53 and pRB

Question 21

Other than mutating the p53 gene, how else can neoplastic cells evade apoptosis?

Answer 21

Neoplastic cells can induce over-expression of the BcL-2 oncogene which encodes for anti-apoptotic BcL-2 proteins

Question 22

How do neoplastic cells achieve ‘replicative immortality’?

Answer 22

Neoplastic cells achieve ‘replicative immortality’ through the expression of telomerase which synthesises telomeres back onto the ends of the chromosomes to prevent the cell from entering senescence

Question 23

Describe the process of tumour angiogenesis

Answer 23

1. Expression of hypoxia inducible factor (HIF-1) by the neoplastic cells is stimulated by hypoxia
2. Hypoxia inducible factor (HIF-1) stimulates the expression of vascular endothelial growth factor (VEGF) which stimulates endothelial growth and proliferation forming sprouts which migrate in the direction of the VEGF being produced by the tumour

Question 24

What are the three main features of tumour vasculature?

Answer 24

Dilated
Tortuous
Permeable

Question 25

What is tumour cell invasion?

Answer 25

Tumour cell invasion is the ability of tumour cells to detach from the primary tumour and invade surrounding tissues

Question 26

What is metastasis?

Answer 26

Metastasis in the spread of neoplastic cells from the point of origin to another part of the body

Question 27

What are the three main routes of metastasis?

Answer 27

Transcoelomic Haematogenous Lymphatic

Question 28

What are the terms used to describe the movement of neoplastic cells into and out of the blood and lymphatic vessels for metastasis?

Answer 28

Intravasation Extravasation

Question 29

Describe the steps of the metastasis cascade

Answer 29

1. Metastatic neoplastic cell detaches from the primary tumour followed by migrating to and invading the basement membrane and stroma via proteolysis 2. Intravasation of the metastatic neoplastic cell 3. Transportation of the metastatic neoplastic cell through the blood or lymphatic vessels 4. Extravasation of the metastatic neoplastic cell 5. Growth and proliferation of the metastatic neoplastic cell at a secondary site

Question 30

What must happen to tumour emboli within blood vessels in order to evade the immune system and continue haematogenous metastasis?

Answer 30

Tumour emboli must become surrounded by host platelets to evade the host immune system

Question 31

Why do neoplastic cells undergo haematogenous metastasis via the veins more than the arteries?

Answer 31

Tumours undergo haematogenous metastasis via the veins more than the arteries because veins have a thinner wall allowing for easier intravasation

Question 32

What are two common venous routes of haemotagenous metastasis?

Answer 32

- Metastasis from the gastrointestinal system to the liver via the hepatic portal system - Metastasis from the heart to the lungs via the vena cava

Question 33

How can adrenal tumours cause sudden death?

Answer 33

Adrenal tumours grow in close proximity to the caudal vena cava and can thus rupture this vein leading to internal haemorrhage and sudden death

Question 34

What is the 'seed and soil' theory?

Answer 34

The 'seed and soil' theory states that neoplastic cells are scattered randomly throughout the body during metastasis but only those that land in a favourable environment survive and proliferate

Question 35

What is the metanistic theory of metastasis?

Answer 35

The metanistic theory states that metastasis is determined by the pattern of blood flow from the anatomical site of the primary tumour to the rest of the body