L16 - TME and cell communication Flashcards
TME
Heterogenous collection of infiltrating and resident host cells, secreted factors and extracellular matrix
Which tissue type is the most cancerous?
Carcinomas - cancers derived from epithelial tissue
> 80%
Fibrosis and collagen: how do they present in the ECM?
Fibroblasts - more solid mass
Collagen - more wavy layered ECM protein
How are data sets of cell types within tissues analysed?
Single-cell RNA sequences
Look at cells within a sample (from a patient) and observe the RNA expressed - by looking at what genes are being expressed, the cell types present can be monitored
Can be used to determine key cell types within a tumour?
Types of cells within the stroma
- Fibroblasts
- Myofibroblasts
- Mesenchymal stem cells
- Endothelial cells
- Fibroblasts
- Pericytes
- Smooth muscle cells
- Mast cells
- Monocytes (immune cells)
- Macrophages (immune cells)
- Lymphocytes
- Adipocytes
- ECM
Fibroblasts: what are they, what do they do, how do they affect cancer, and what are they activated by which causes them to turn into CAF?
Key component of the tumour stroma
Secrete things that change the properties of the microenvironment and promote tumour growth:
* Growth factors
* Cytokines
* ECM components
Physical barrier formed around the tumour, preventing immune cell entry
- TGF-beta
- PDGF
- Fibroblast growth factor 2 (FGF2)
Are fibroblasts a uniform collection of cells?
No, they represent a heterogenous collection of cells - the same oncogene may cause various different variations instead
This is because different parts of the body have different gene expressions from their fibroblasts
aSMA: what is it and what does it do?
Alpha-smooth muscle actin - cytoskeletal protein within CAFs
Can be stained and used to detect CAF presence
ECM: add more later
Glycan modification is implicated in cancer progression
Glycan modification is implicated in cancer progression
Rate-limigting step in tumour formation
Stromal cells and ECM - for cancer to advance, cells in the TME must become tumour promoting and cause increased proliferation, invasion, and intravasation
Fibroblast-rich stroma replaced by myofibrobalsts - generates collagen desmoplastic stroma
How do stroma and tumour cells interact to promote cancer?
Stromal cells are recruited (ie through PDGF) and exploited by cancer cells to promote cancer growth (secreting IGFs (insulin-like growth factors))
Heterotypic signalling
Communication between dissimilar cell types
- Mitogenic growth factors - HGF, PDGF, TGF-alpha
- Growth inhibitors - TGF-beta
- Trophic factors - IGF-1, IGF-2
Juxtacrine
Receptor-receptor signalling - through desmosomes etc
