Metastasis Flashcards
What increases in expression in invasive human tumours?
Twist, snail, slug, SIP1, vimentin.
What are the three mechanisms by which E cadherin expression is reduced?
Gf mediated up regulation of repressors (Snail, twist, ZEBS)
E cadherin mutation - non functional
Reduction in expression due to genomic modifications targeting e cadherin promoter.
What is N cadherin?
De novo expression in tumours facilitates interaction with stromal cells and promotes migration.
What are membrane type MMPs?
What is MMP-9?
Membrane bound - target secreted MMPs and surface expression activates the secreted MMPs e.g MMP14 targets MMP-2
Gelatinise B - type IV collagenase.
How does the balance of MMP activation become shifted?
UPa activates plasmin
UPa binds PM receptors and also upregulated in invasive tumours.
Receptor binding focuses proteolytic activity at surface.
Tumour cells induce fibroblasts to make MMPs.
What do RGD peptides do?
Recognised by integrins
Block formation of lung modules in experimental metastasis assay (prevent functional activity of integrins cells –> can’t metastasise).
What is the current thought concerning tumour associated macrophages and intravasation?
Macrophages promote migration and may help hold endothelial cells open.
How can defends mechanisms promote survival?
Lymphocyte induced clumping shield innermost cells from trauma.
Monocytes and platelets - provide angiogenic cytokines.
Neutrophils provide proteolytic enzymes.
Give one reason breast likely to find soil in lung
Melanoma in skin
Ligand CXCL12 in lung and receptor CXCR4 in breast.
Melanoma has CCR10 receptor
Skin has CCL27 ligand.
How efficient is metastasis?
Inefficient
Only 1 out of every 10,000 cells that initiate it form one.
But only need one or two to establish micrometastasis at a distal site.
