Invasion and metastasis Flashcards
What are the 6 steps of the invasion-metastasis cascade?
1) Local invasion
2) Intravasation
3) Migration
4) Extravasation
5) Micrometastasis
6) Colonisation
What is local invasion?
Primary cancer cells invade the surrounding tissue
What is intravasation
Cancer cells enter the circulatory system
What is migration?
Haematogenous transit to distant sites and survival during process
What is extravasation?
Cancer cells exit through the vascular wall into the secondary host site
What is micrometastasis?
The founding of microscopic colonies of cancer cells
What is colonisation?
Cancer cell outgrowth into a tumour of macroscopic size.
What does the metastatic process rely heavily on>
The interaction between cancer cells and their surrounding tumour microenvironment.
What are the types of cancer cell interactions that can occur with the tumour microenvironment?
Contact dependent: Cell-cell and cell-ECM adhesion molecules
Contact independent - Soluble molecules including growth factors, chemokines and cytokines.
What needs to change in a cancer cell for dissemination to occur?
Needs to lose genes that helped it grow in an organised structure alongside the rest of the tumour. Needs to express proteins that can degrade components of the extracellular matrix and proteins that increase invasiveness and motility
What process is key for local invasion and dissemination?
EMT
What triggers EMT?
Epigenetic/genetic changes and heterotypic signals from the stroma (TGFb, Wnt)
What is required for EMT orchestration?
A series of master EMT-inducing transcription factors (Snail, slug, twist)
Is EMT reversible?
Yes - MET
What cellular features change during EMT?
Lose cell polarity (cadherin switch)
Lose cell adhesion (Cadherin, integrin, CD44)
They become isolate motile cells (HGF/SF)
They are able to modulate their environment (MMPs, proteases)
Why is EMT in metastasis not a binary switch?
Because EMT has been reported in collective migration of cells during dissemination. Therefore partial EMT allows cancer cells to gain EMT features whilst maintaining epithelial traits.