Final Flashcards
what is stroma
- tumor microenvironment
- refers to everything in the tumor environment that does not include non-neoplastic cells
What are the cell types
- immune cells
- fibroblasts (connective tissue)
- endothelial cells (blood vessels)
- adipocytes (fat tissue)
what is the extracellular components of the stroma
extra-cellular matrix (ECM)
What is the ECM made of?
secreted proteoglycans (proteins with added sugars)
what does the stroma play an active role in?
in development and maintenance of tumors
neoplastic and non-neoplastic cells are present in comparable number (50/50) in what kind of tumor
carcinomas
what is the pdx model
Transplantation of human cancer cells into live mice
why is the pdx model typically done
to model an in vivo microenvironment
- because tissue culture plastic (in vitro models) do not accurately recapitulate a tumor microenvironment
definition of heterotypic signaling
communication between dissimilar cell types
generally, what do cancer cells release
chemokines and growth factors that attract stromal cells and cause the proliferation of stromal cells
what do stromal cells contain
receptors for growth factors that cancer cells release
neoangiogenesis
formation of new blood vessels
What do stromal cells release
growth factors that cause the proliferation of cancer cells
what do cancer cells contain
receptors for growth factors that stromal cells release
endothelial cells
cells that line blood vessels and capillaries (smaller blood vessels)
pericytes
the outer layer of blood vessels and capillaries (support blood vessels)
angiogenesis signlaing
epithelial cells and stromal cells signal endothelial cells to proliferate
what do endothelial cells secrete
growth factors and attract pericytes
what do pericytes secrete
pro-survival signals to endothelial cells (including VEGF1)
what does heterotypic signaling generally promote
the development and maintenance of blood vessels in tumors
capillaries in tumors are constructed _____ compared to normal tissues
haphazardly
characteristics of tumor capillaries
- pericytes do not completely cover the capillaries
- pericytes are more loosely associated with the capillaries
- endothelial cells do not form a continuous sheet; there are gaps between neighboring cells
- tumor capillaries are 3x bigger than normal capillaries
- results in leakage of fluid into tumor microenvironment
- causes tumors to have high hydrostatic pressure
- complicates delivery of anti-cancer therapeutic drugs
- prevent formation of pressure-gradient
what does the hazardous formation of tumor capillaries result in
results in inefficient transfer of anti-cancer therapeutic drugs to the site of the tumor (anti-cancer drugs would preferentially accumulate in normal tissue compared to tumor tissue)
similarities between wound healing and angiogenesis
- recruitment of stromal cells
- stromal cells recruit and activate endothelial cells
- immune cells
what do stromal cells recruit and activate
endothelial cells
- partially because stromal cells secrete VEGF
- which stimulates neoangiogenesis
what do immune cells promote
neoangiogenesis via VEGF
what do immune cells secrete
MMPs (matric metalloproteases) which release growth factors tethered to the ECM
angiogenic switch
a property that pre-malignant cells must acquire to be able to form a tumor
most normal cells do not have the ability to…
make blood vessels around them (promote neoangiogenesis)
in order for a cancer cell to progress towards malignancy they must first acquire
the ability to make blood vessels around them (promote neoangiogenesis)
what is an example of the angiogenic switch
RIP-tag mouse model of pancreatic cancer (beta cells)