cancer angiogenesis and metastasis Flashcards
—- is the spread of tumour cells from a primary site and their establishment at distant secondary locations majority of cancer patients die because of this
metastasis
- tumor can spread via —-
- metastasis is a complex — process
- Failure to complete any of the steps prevents —- formation
- —- of tumour cells leaving the primary tumour complete all steps to successfully form metastasis
- after 24 h in circulation less than —of tumour cells are still viable; less than — survive to form metastases ( but it only takes one cell)
blood , lymph , within body cavity ( transoelomic)
multi step
metastasis
small %
0.1%
0.001%
- Metastasis can occur on the basis of — so — tumours have a higher chance of metastasis e.g. —-
- Metastasis can occur before the cancer has grown to a — (soon after initiation) e.g. small cell lung cancer
- Metastasis can be extremely —- or does not happen at all e.g. basal cell carcinoma of the skin
- which means metastasis development has —-
size
large
breast n colon
detectable size
infrequenct
has no rule
where do metastases go:
primary : site of metastasis
breast :
prostate :
stomach :
colon:
melanoma:
bone n brain
bone
liver n ovary
liver n lungs
brain liver n bowel
organ specificity :
1- mechanistic theory ( Ewing) refers to first site to which a cancer metastasizes is the closest one in which there are —-
2- seed and soil theory refers to – Cells (seeds) are dispersed — but only grow inorgans which provide the correct — necessary for growth of that particular tumour (fertile soil)
* Regional metastases can be attributed to —- & — factors (support Ewing’s theory) but — organ metastases is specific (Paget’s theory).
* Both are probably factors in determining to which organ a cancer can metastasise
small blood vessels
randomly
factors
anatomic and mechanical
distant
steps of metastatis:
colonal expansion —> carcinoma in situ –> invasion —< dissemination —< micrometastatis —> angiogenesis —> metastatic tumours
key steps of metastasis:
1- distribution of — and —- and degradation of —
2- — and — through storm
3- intravastion into — or —-
4- —- in circulation
5- — out of blood or lymph vessels and — into new tissue
6- — in new tissue
7- once tumour reached certain size , development of new — aka —
cell- cell and cell-matrix
ECM
invasion n migration
blood or lymph vessels
survival
extraversion
migration
new blood vessels aka angiogenesis
— is a criteria of metastasis and its defined in 3 major steps:
1. —- : cell adhesion molecules -
integrins
2. —- : enzymes - MMPs, uPA
3. —- : motility factors
invasion
attachment
proteolysis
migration
metastasis requires — by which its new blood vessels form from pre-existing vasculature
angiogenesis
- Critical for growth and metastasis of solid tumours - supply — and — to tumour and remove — products
- In the healthy adult, limited new vessel formation, e.g. —-
- New vessels in tumour also facilitate –
- In tumours, new vessels are formed by —
1- —- = sprouting of new vessels from pre-existing
vasculature
2- —– = de novo vessel synthesis from endothelial progenitor cells (EPCs) - first vessels in developing embryo
oxygen n nutrients
waste
wound healing
metastasis.
angiogenesis and/or vasculogenesis
angiogenesis
vasculogenesis ( aka occurs from scratch )
steps in angiogenesis:
1. Secretion of — by tumour cells (e.g.VEGF)
2. Release of — from “activated” endothelial cells
3. —- of blood vessel wall & release of — cells
4. Migration of the endothelial
cells into the — and into the —
5. endothelial cell —
6. — formation
7. — of newly formed vessels
8. Initiation of —
angiogenic factors
protease
permeabilisation
vascular endothelial
interstitial space
tumour
proliferation
lumen
fusion
blood flow
Tumours produce — that stimulate angiogenesis, others induce surrounding normal cells to do so.
1- pro - angiogenic factors as — and — factors which include:
2- other factors as:
growth factors
cytokines n growth factors as:
– Vascular endothelial growth factor (VEGF)*
– Epidermal growth factor (EGF)
– Platelet-derived growth factor (PDGF)
– Transforming growth factor a (TGFa)
other factors are:
– Hypoxia
– Oncogene activation
– Loss of tumour suppressor genes e.g. p53, VHL
- angiogenesis is stimulated by —
- Solid tumours develop regions of – as their growth outstrips — growth and –
hypoxia
blood vessels and oxygen supply
hypoxia :
- stimulates —
- impairs —
- selects for more —
- As hypoxic cells are not actively — they are inherently resistant to — (which targets dividing cells)
angiogenesis
drug delivery
more aggressive cells
proliferating
chemo
angiogenesis inhibitors include :
- Angiostatin (cleavage fragment of plasminogen)
- Endostatin (cleavage fragment of collagen XVIII)
- Interferons
- Platelet factor 4
- TIMPs (tissue inhibitor of metalloproteinases)
