L25: The Tumour Microenvironment Flashcards
What does the tumour micro-environment look like
It contains many non-malignant cells
What are the non malignant cells found in the micro-environment
Cancer associated fibroblasts Pericytes Endothelial cells Myeloid cells Lymphocytes Extra-cellular matrix i.e collagen
What happens to the stromal cells as the tumour cells develop
Become abnormal
Is tumourigensis and stormagensis independent processes
Yet but occur at the same time i.e cancer cells promote priming of stroma and primed stroma support the tumour growth (like a cycle)
Does cancer have inflammation
Yes
What can reduce inflammation and therefore the risk of cancer
NSAID
Cox-2 inhibitors
In Hodgkin lymphoma what are the malignant cells surrounded by
Non tumour components
What does Hodgkin cells provide to the non tumour cells
Growth signals to non tumour cells so they can proliferate
What does non tumour cells provide to the Hodgkin cells
Growth signal to the Hodgkin cell so it survivors
Which cells in the tumour micro-environment are capable of killing the tumour
Cytotoxic T cell
Natural killer cells
What is the role of cytotoxic T cells
Recognise cancer antigens on the tumour cell and kill them
If there are immune cells that can kill tumours cell in the micro-environment why is there immunosupression
Due to the production of cytokine by the tumour cells so cytotoxic T cell and natural killer cells are overwhelmed by the number of cell that oppose their response
Which cell can prevent cytotoxic T cells from killing the tumour cell
T regulatory cells
How is the tumour micro environment recruited
Via 2 lipids called:
Lysophosphatidic acid
Sphingosine 1 phosphate
What does lysophosphatidic acid promote
Lymphocyte entry
What does sphingosine 1 phosphate promote
Lymphocyte retention
Therefore what are patients with hodgkin lymphoma have less lymphocytes in the blood
They become retained in the tissue due to sphingosine 1 phosphate
What other soluble factors does cancer cells produce
PDGF
What is PDGF involved in
Differentiate fibroblast to myofibroblast
Recruit macrophages
Activate myofibroblast
What are myofibroblasts
Altered forms of fibroblasts
What does myofibroblast produce
Collagen and matrix proteins
What are myofibroblast important for
Wound healing
How do myofibroblast contribute to cancer cancer
Produce collagen and immunosupressive factors such as:
TGF beta
HGF- growth factor
VEGF- angiogenesis
MMPS- degrade basement membrane important for EMT i.e metastasis
How does collagen promote tumour growth
1) There is expression of collagen receptor called discoidin domain receptor 1 (DDR1) which is an oncogene cell tyrosine kinase that binds to collagen
2) when collagen binds to DDR1 conformational change occurs
3) downstream signalling occurs for growth
In cancer what are the 2 main macrophages
M1 macrophages
M2 macrophages
What are M1 macrophages
Anti tumour activity that defect action bacteria and cause immunostimulation
What are M2 macrophages involved in
Angiogensis and tissue remodelling for tumour promotion
Downregulate M1 macrophages
Associated with cancer
What happens to fibroblast when they are acitvated in cancer
Become cancer associated fibroblast
Give an example of a cancer associated fibroblast
Myofibroblast
What other factors does cancer associated fibroblast produce that cause scarring
Extracellular matrix
Why do many cancer cells how lymphoneia i.e low lymphocytes
Due to expression of sphingosine 1 phosphate that causes retention of the lymphocyte
