Lecture 8 - Invasion and Metastasis

Question 1

Define invasion

Answer 1

Infiltration of local tissue by cancer cells

Question 2

Define metastasis

Answer 2

Secondary tumour that grows at a site distant from the primary tumour. Arises from detached, transported cancer cells

Question 3

Outline the metastasis pathway (assuming blood transport)

Answer 3

1) Primary tumour formation
2) Invasion
3) Intravasation
4) Transport through blood
5) Arrest in microvasculature of organ(s)
6) Extravasation
7) Micromets
8) Colonisation - 2ndary tumour

Question 4

How do tumour cells and local host cells interact?

Answer 4

Form paracrine loop - ligand from one activates receptor on the other and vice versa
Drives migration

Question 5

What must be disrupted in order for metastasis to occur?

Answer 5

Cell to cell adhesion

Question 6

What process helps to promote cell motility?

Answer 6

Epithelial to mesenchymal transition

Results in decreased cadherins - aids motility

Question 7

What is the difference between early and late dissemination?

Answer 7

Early - cells break away before primary tumour establishes - from premalignant cell
Late - cells break off from established primary tumour

Question 8

What are the different modes of migration?

Answer 8

• Mesenchymal cells (arise from EMT) undergo fibroblastic movement
• Amoeboid cells (arise from MAT) undergo amoeboid movement - highly efficient

Question 9

What is special about integrins?

Answer 9

Transmembrane receptors which show bi-directional signalling

• Outside-in - ligand binds on outside, signal inside
• Inside-out - ligand binds on inside, signal outside - cell adhesion/migration

Question 10

How does hypoxia drive angiogenesis?

Answer 10

Hypoxia drives angiogenesis via hypoxia inducible factors which increase the transcription of vascular endothelial growth factors

Question 11

How does colonisation occur?

Answer 11

Via:

• Attaching to endothelial surface
• Rolling
• Spreading
• Extravasating