Term
| Stimulation of angiogenesis |
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Definition
Hypoxia -> HIF(TF) -> VEGF and bFGF
VEGF binds to VEGFR(RTK)
Causes endothelial cells to proliferate
New vessels stabilized by pericytes |
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Term
|
Definition
MMPs(collagenases) are released to
degrade ECM
TIMP(proteinase inhibitor) inhibits MMPs |
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Term
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Definition
Under normoxia Proline hydroxylase adds
OH to HIF-1 -> HIF-OH
pVHL binds HIF-1-OH. ubiquinates
Hypoxia. pVHL does not bind and inhibit
HIF |
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Term
| von Hippel-Linadau(VHL) syndrome |
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Definition
AD. Multiple hemangioblastomas of retina
VHL normally (inhibits)ubquinates HIF-1
HIF-1 dimerizes and induces VEGF regardless of O2 availibilty. |
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Term
|
Definition
3x more common in females
Increase in VEGF, bfGF. Decrease in
inhibitors
Strawberry skin* |
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Term
| Drug Targetting of angiogenic GF and GFRs |
|
Definition
VEGF: bevacizumab(Avastin) inhibits
Thrombospondin: angeiogenesis inhibitor
Thrombospondin secretes FasL
FasL - FasR = apoptosis(extrinsic)
Will only kill new blood vessels
Endostatin: Stabilizes new BVwall
Inhibits new vessel sprouting |
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Term
|
Definition
| increase in angiostatin and endostatin |
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Term
|
Definition
Loss of E-cadherin(cell-cell)
Attachment to ECM: Increase in CD 44
hyaluronon binding protein(Binds mmp) |
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Term
|
Definition
Degradation of ECM:
Serine proteases(uPA, tPA)
Plasminogen-> plasmin -> MMps
Digests ECM and clots
MMPs: TIMP unbalanced at invading edge
MMPs degradation of ECM reveals cryptic
sites(laminin -> chemotactic factor) |
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Term
|
Definition
Tumor Motiliy factors: AMF, HGF< EGF
Signal via Rho GTPases; Rho,Rac, Cdc42.
Changes in cytoskeleton -> movement
Intravasation:
VEGF -> endocytosis of VE-cadherin.
Increase in vascular permeability.
Increased entry of tumor cells |
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Term
| Chemokine regulation of breast cancer |
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Definition
CXCR4 binds CXCL12
CCR7 binds CCL21 |
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Term
Summary of changes during metastatis
(migration)
Increase / Decrease of what? |
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Definition
Increase:
VEGF, bfGF, PDGF, EGF, HGF
Integrins
proteases(MMPs)
Decrease:
Cell-Cell adhesion's(cadherins)
ECM proteins
Protease inhibitors(TIMPs) |
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