Spread of Tumours

Question 1

How does a tumour develop a blood supply?

Answer 1

• When a tumour becomes enlarged it becomes hypoxic
• Hypoxic environments can select for fitter variants
• cellular response to hypoxia is transcriptional and mostly mediated by HIF-1

Question 2

What is the structure of HIF-1?

Answer 2

Heterodimeric made up of HIF-1α and HIF-1β

Question 3

What is HIF1 activity dependent on?

Answer 3

HIF-1α avaliability

Question 4

What kind of molecule is HIF1?

Answer 4

Transcription factor

Question 5

Why does HIF1 increase angiogenesis?

Answer 5

VEGF is a direct target of HIF1 and stimulates angiogenesis

Question 6

Under normal conditions what happens to HIF-1α?

Answer 6

• Normally modified by hydroxylation of proline residues which requires O₂
• Once hydroxylated it is marked for ubiquitination and is degraded

Question 7

What can inhibit HIF-1α formation?

Answer 7

ROS

Question 8

What happens to anti-angiogenesis factors in cancer cells?

Answer 8

Reduced in tumour cells

Question 9

What is anoikis?

Answer 9

Cell death induce by loss of anchorage to the cell substrate or ECM

Question 10

What steps are required for a primary cancer to become metastatic?

Answer 10

1. Resistance to anoikis
2. Invasion
3. Metastasis

Question 11

How do metastatic cells become resistant to anoikis?

Answer 11

Through increased expression of anti-apoptotic genes

Question 12

What are the steps in invasion of a cancer cell?

Answer 12

1. Tumour cells invase surrounding tissue into lymphatic system or blood supply
2. Travels to organs
3. Survives in hostile environment to grow into metastatic tumour

Question 13

What is epithelial to mesenchymal transition?

Answer 13

Cells acqure properties of mesenchymal cells and become more mobile

Question 14

What occurs in epithelial to mesenchymal transition?

Answer 14

• Attachment to extracellular matrix
• Local proteolysis to destroy basement membrane and ECM
• Tumour cell movement into region of matrix modified by proteolysis

Question 15

Why do primary tumours often metastise to specific organs?

Answer 15

• Easy access via circulation from primary tumour
• Seed and soil hypothesis

Question 16

What is the seed and soil hypothesis?

Answer 16

• Some tumour cells require specific growth factors which are present in some tissues but not in others

Question 17

Why do such a small percentage of tumour cells not survive in circulation?

Answer 17

• Mechanical sheer force
• Destruction by NKs
• O2 toxicity

Question 18

What experiment has been done to show that metastasis occurs earlier than previously thought?

Answer 18

• Label tumour cells in mouse
• Cells can be detected in blood stream before primary tumour acquires pathological features associated with metastasis