cancer mechanisms review deck Flashcards
what are stromal cells?
supporting cells that form the tumor “microenvironment”
what is the significance of the layer laid down by fibroblasts around tumor?
breaking through this layer = mets
ex about melanoma cells and stromal cells
- melanoma cells secrete PDGF
- PDGF stimulates release of IGF-2 from stromal fibroblasts
- IGF-2 is a survival factor for melanoma cells
what is the “angiogenic switch”?
controls a tumor’s ability to increase blood vessels
what is the trend regarding bv density in a tumor and patient survival?
decreased bv density correlates with increased pt survival
what happens with HIF1a during hypoxia?
during hypoxia, HIF1a stimulates VEGF = proliferation of endothelial cells
what happens with HIF1a during normoxia?
during normoxia, HIF1a is hydroxylated by proline hydrroxylase, then recognized by VHL, ubiquitinated and degraded
what are the 4 difference between normal capillaries and tumor capillaries
- larger diameter
- loose pericytes
- end blindly or double back
- leaky (implication for mets)
describe local invasion
cells break away from primary tumor through disruption of cell to cell interactions/cell-ECM interactions and leaky capillaries
describe intravasation
cells enter blood or lymph circulation, secondary to changes in cytoskeleton (actin-WASP) and MMP
what is the action of WASP (actin) in intravasation?
aide with the formation of invadopodia
what is the action of matrix metalloproteases in intravasation?
MMPs facilitate the breakdown of ECM and basement membrane
describe TGF-b and MMP
TGF-b –> PAI-1 –> inhibit MMP
loss of TGF-b yields increased MMP
describe extravasation
cell reaches capillary that limits movement and moves out of vessel into tissue, mesenchymal properties help with this
what is needed for micro mets to become macro mets?
correct stromal environment
