angiogenesis Flashcards

1
Q

hypoxia

A

low oxygen on tissue

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2
Q

what do cancers need to grow?

A

oxygen, glucose, amino acids, vascular system

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3
Q

what is a pericyte?

A

support cell for small vessels

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4
Q

what is the stroma made of

A

fibroblasts and other cell types

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5
Q

what happens at the cell cell junctions of endothelial cells?

A

there is increased permeability so cells can leave the blood as well as fluids and solutes

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6
Q

what does it mean when you say oxygen has a diffusive limit

A

it cannot diffuse forever

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7
Q

how close are cells to a blood vessel in the venous end

A

10µm because the blood is deoxygenated so we need a short diffusion distance

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8
Q

how close are cells to a blood vessel in the arterial end

A

70µm because the blood is oxygenated

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9
Q

how do cancers stay oxygenated (6)

A
  1. induce vasodilation
  2. sprouting angiogenesis
  3. intussusceptive angiogenesis
  4. anaerobic metabolism
  5. vascular co-option
  6. vasculogenesis
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10
Q

what is intussusceptive angiogenesis

A

splitting existing blood vessels

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11
Q

what is vascular co-option?

A

when cancers grow along blood vessels

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12
Q

what is vasculogenesis

A

developing new vessels de novo (spontaneously)

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13
Q

what does VEGF stand for

A

vascular endothelial growth factor

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14
Q

what does VEGF do

A

makes vascular endothelial cells grow

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15
Q

VEGF-A structure

A

glycosylated protein, 121-189 amino acids long

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16
Q

summary of the process of angiogenesis

A

VEGF production and secretion, endothelial activation - binds to a receptor and induces Ca2+ uptake in the cell and other cellular pathways. Increase in permeability, matrix degradation, this allows pericyte withdrawal, new blood vessel spout forms and endothelial migration occurs, cell division behind migrating sprout, lumen formation, sprout connection and blood flow

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17
Q

what

A

It also activates standard map kinase ras signalling

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18
Q

what happens to the O2 in the cell as it proliferates

A

the amount of it is reduced

19
Q

what does the reduction of O2 in the cell activate

A

Transcription factor HIF1 (hypoxia inducible factor)

20
Q

what happens when HIF1 is activated

A

translocated to nucleus and turns on and off any genes, including VEGF, VEGF is produced and secreted, it activates VEGFR (VEGF receptor) which activates endothelial cells

21
Q

what are the different isoforms of HIF1

A

HIF1-α and HIF1-β

22
Q

what happens to HIF1-α in normal conditions

A

it is rapidly degraded by oxygen

23
Q

what happens to HIF1-α in hypoxic conditions

A

it binds to HIF1-β to form a
transcription factor complex which has slowed degradation

24
Q

what is the hypoxia response element

A

region of DNA with a particular sequence that the HIF complex can recognise

25
what happens when the HIF complex comes across the hypoxia response element
it binds to the sequence and then further transcription factors can bind and form a big complex which can go along and make mRNA for protein production
26
what TF binds after the HIF complex binds
TBP (Tata binding protein)
27
what does TBP do
finds the polymerase II
28
what happens when TBP and polymerase II bind
they can turn genes on and off
29
what happens to glucose transporters in hypoxia
they can be turned on and off so that the cell can overload itself with glucose so it can respire by glycolysis
30
how are the effects of VEGF reduced
with a VEGF antibody
31
how does VEGF cause leakiness
1. blood flow (more blood more leak) 2. angiogenesis - growing more leaky blood vessels 3. increase vascular permeability (make specific vessels leaky)
32
what does the VEGF mechanism depend on
Ca2+
33
how does VEGF weaken vessel walls
it enhances proteinase activity
34
what happens in pericyte withdrawal
the pericytes move away from the blood vessel, creating space for the endothelial cells to migrate
35
intussusception (1st type of angiogenesis)
fibroblasts and pericytes push in on endothelial cell and so it becomes 2 separate vessels which move apart
36
sprouting angiogenesis (2nd type)
endothelial cells put out filopodia towards sources of VEGF (tip cell)
36
which cells divide in sprouting angiogenesis
the stalk cells (directly behind the tip cell)
37
how does only one sprout occur and not many
tip cells repress the cells around them and stop them from being able to become tip cells
37
what happens when 2 filopodia meet
they signal to the other cells that they have found another tip cell, the sprouts grow closer to each other and then the tip cells differentiate into endothelial cells to make a vascular loop
38
what does angiopoietin 1 (ang1) do
stabilises vessels, opposite of VEGF
39
what does angiopoietin 2 (ang2) do
destabilises vessels, blocks effects of ang1
40
what does platelet derived growth factor do (PDGF)
recruits pericytes
41
what is bevacizumab (Avastin)
a drug that binds to circulating VEGF
42
what is Ramucirumab
an antibody that binds to the VEGF receptor, inhibiting its activation