Invasion & metastasis

Question 1

Why do cancer cell metastasis

Answer 1

Because the environment isn’t favorable enough anymore, regarding:

• Hypoxia
• Space
• Nutrient
• Get signals like; Wnt, E-cadherin etc. or epigenetic changes

Question 2

Explain the 6 steps of Metastasis

Answer 2

1. localized invasion
   - Cancer cell go through EMT (epithelial to mesenchymal transformation)
   - They also need to develop proteases that degrade the basement membrane
2. Intravasation
   get into the blood and start circulating, the cells get help from immune system to be kept in a mesenchymal phenotype in the blood
3. Get into a new organ
   Adhere to the vessel walls or get stuck in capillary network. “seed and soil theory” chemokine and receptors direct they way for cancer cells into new organs favorable for their origin (gene signature)
4. Get out of the blood vessel
5. Form micrometastasis
   Small clusters of cancer cells stay near the vessel wall and allow the tumor to be dormant for years
6. Form macrometastasis
   EMT–>MET transformation allow epithelial cancer cells to colonize and grow

Question 3

Explain the EMT MET process

Answer 3

EMT –> MET

1. Epithelial cell looses its tight-junction to other cells since some signals like E-cadherin is lost, thereby starting to de-attach. Collectively getting growth signals, cytokines etc. (EMT effectors)
2. The epithelial cell looses its adherens-junctions and become a mesenchymal cell, expressing fibronectin, vimentin etc.

MET–> EMT

3. When the mesenchymal cell landed on a new spot it starting to express E-cadherin and adhesive contact
4. The mesenchymal cell start to create adhesion and thigh-junctions and become an epithelial cell