Angiogenesis and EMT Flashcards
define angiogenesis
formation of new blood vessels
angiogenesis is aka
neovascularization
what proteins do cells secrete that stimulate the growth and spread of new blood vessels
VEGF & bFGF
what does VEGF stand for
vascular endothelial growth factor
what does bFGF stand for
basic fibroblast growth factor
in the experiment with a rabbit’s eye where were the tumor cells implanted that proved tumor growth was dependent on angiogenesis
- anterior chamber of the eye (no growth)
- iris of the eye (blood vessel growth & increased tumor size)
what was suggested after observing vessel growth when cancer cells were placed within a non-permeable membrane
cancer cells produced an agent that diffused through the membrane, inducing angiogenesis
describe the steps of VEGF triggering angiogenesis
cancer cells secrete VEGF -> VEGF binds to receptors on endothelial cells -> signal transduction proteins promote gene expression & cell response
what cell responses occur due to VEGF triggering angiogenesis
- proliferation of endothelial cells
- secretion of MMPs
what do MMPs stand for
matrix metalloproteinases
what is the function of MMPs
- degrade extracellular matrix
- contribute to metastasis
what are some additional functions of VEGF
- formation of capillaries and lymph ducts
- capillary permeability
- regulation of endothelial cells
- monocyte migration
- hematopoiesis
- recruitment of hematopoietic progenitor cells from bone marrow
what are 2 other forms of neovascularization
- vasculogenic mimicry
- vasculogenesis
define vasculogenic mimicry
melanoma cells form vascular-like structures
define vasculogenesis
endothelial progenitor cells differentiate and proliferate
most _____ consist of epithelial cancer cells and recruited ___ cells
carcinomas
stromal
what do carcinomas depend on for support
stromal cells
what is critical for supporting angiogenesis and metastasis
the extracellular matrix (ECM)
what are critical components of the stroma
endothelial cells
what do endothelial cells secrete
PDGF
what do PDFGs recruit
pericytes which help build outer capillary walls
what enables tumor cells to stimulate wound healing response
heterotypic signaling
list the 4 stages of EMT
- loss of tight junctions
- cytoskeletal changes/ formation of stress fibers
- suppression of epithelial genes and activation of mesenchymal genes
- increased motility and migration
what does EMT enable cancer cells to do
invade the basal layer
what is secreted that enables degradation of ECM making space for proliferation and metastasis
MMPs and TGF-B
what does MET allow
the reestablishment of tumors (metastasis)
what are some examples of angiogenic factors
- VEGF
- TGF-B
- PDGF
what will endothelial cells stimulated by angiogenics express
FAS death receptor
what is the function of thrombospondin (TSP-1)
releases FasL launching apoptosis
antiangiogenics target ____________ more effectively than __________ vasculature
- neovascularization
- established
list some examples of endogenous inhibitors of angiogenesis
- endostatin
- angiostatin
- vasostatin
what is the most common type of anti-angiogenic drug
avastin
avastin’s activity…
anti-VEGF-A
what points of the VEGF pathway are targets of therapeutic agents
- ligand binding
- VEGF receptor
- endothelial proliferation
explain the effects of targeting cancer w/ PDGF receptor inhibitor
- pericyte protection is impaired
- endothelial cells are sensitive to VEGF-R inhibition and chemotherapy
what was a treatment discussed for neovascularization
combretastatin
what is vascular targeting by nanotechnology
nanoparticles have a ligand -> mutant raf gene is internalized inhibiting the raf pathway of angiogenesis
what are the 2 limitations of treatment of neovascularization
- tumor cells may cause necrosis
- tumors may return more aggressive and invasive
