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Cancer Cell Biology > 12 - Angiogenesis > Flashcards

12 - Angiogenesis Flashcards

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1
Q

What is the “cut-off” size of a tumor where it will be able to receive efficient oxygen and nutrients by diffusion from host vasculature? What happens when the tumors outgrow this size?

A

1 cubic mm | bigger tumors = outgrow O2/nutrient supply = begin to starve and become hypoxic = need more &raquo_space;> will secrete angiogenic factors

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2
Q

What are endothelial cells in relation to blood vessels?

A

cells that make up the vessel walls | these are the ones that divide and grow towards tumor to feed it

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3
Q

How do endothelial cells divide and grow?

A

in response to angiogenic factors and they must have the receptor in order to respond to it

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4
Q

What is the main angiogenic factor discussed?

A

VEGF

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5
Q

What are the 3 goals of endothelial cells during angiogenic events?

A

divide | migrate | survive

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6
Q

How do hypoxic tumor cells cope with hypoxia?

A

gaining more mutations = become genetically unstable

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7
Q

What is perfusion?

A

amount of fluid pushed through tissue | the more we have = the better (bc it is carrying O2 and nutrients)

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8
Q

What is HIF1-a? What is it’s function?

A

transcription factor | induces expression of VEGF and turns on genes with hypoxia response elements

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9
Q

What happens to HIF1-a in the presence of O2?

A

PHD hydrolates (OH) HIF1-a &raquo_space;> VHL ubiquitin tags it for degradation

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10
Q

What is PHD?

A

proline hydroxylation = hydrolates proteins

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11
Q

What is VHL?

A

a ubiquitin ligase

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12
Q

What happens to HIF1-a in the absence of O2?

A

PHD proteins can’t put OH on HIF1-a bc no O2 present &raquo_space;> HIF1-a goes into nucleus and turns genes on

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13
Q

On which promoters within the DNA will HIF1-a sit on?

A

hypoxia response elements (HRE)

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14
Q

What are the 4 types of genes that HIF1-a expresses in order to cope with hypoxia?

A

metabolism | vascular | iron/erythropoeisis | proliferation/survival | many others

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15
Q

In which cancer(s) are HIF1-a never or rarely expressed and why?

A

in melanoma because it’s skin and there is enough O2 on surface

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16
Q

What are 2 physiological characteristics (ie: hot, cold, basic, etc) are tumor cells?

A

hypoxic and acidic

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17
Q

What is ion trapping?

A

H+ ions trapped by chemotherapeutic drugs

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18
Q

Why would a chemotherapeutic drug that is basic will not work?

A

it will be neutralized in the acidic aggressive tumor cells = rendered ineffective

19
Q

What is VEGF?

A

angiogenic growth factor | many isoforms (common one = VEGF-A) | dimer

20
Q

What does expression of VEGF correlate within cancer patients? Why?

A

poor prognosis

21
Q

What is the quality of the vessels tumor cells form? (4 things)

A

poor quality | leaky (dilated) | twisted | unstable = can easily fall apart without VEGF constantly present

22
Q

What do the vessels that tumor cells make require in order to sustain its shape and not collapse?

A

constant stimulation of VEGF

23
Q

If you are making VEGF, it is because you want to do what?

A

make more blood vessels

24
Q

When would we make VEGF?

A

during growth development (childhood) | major injuries that destroy vessels

25
Q

What cells replenish connective tissue?

A

fibroblasts

26
Q

What cells replenish the epithelial cells?

A

adult stem cells

27
Q

What does VEGF induce within the epithelial cell in order to move and migrate?

A

actin polymerization

28
Q

In what 2 ways can vessels grow?

A

series or parallel

29
Q

How do vessels growing in parallel affect perfusion?

A

less length = less friction = less resistance = more perfusion

30
Q

How do vessels growing in series affect perfusion?

A

more length = more resistance = more pressure in vessels = increase chances of leaking = less perfusion

31
Q

Tumors don’t have a uniform distribution of blood vessels, how does this affect drug treatments?

A

only well-vascularized tumor cells will get hit with the drug more than those that are less vascularized

32
Q

If we do an anti-angiogenic drug, does it hurt the patient?

A

must analyze the perfusion to dictate if we are affecting anything | perfusion change = unaffected BUT affects the vasculature

33
Q

Are there any natural occurring cells/proteins that inhibit angiogenesis?

A

family of proteins | tissue inhibitors - metalloproteases

34
Q

What is TIMP3?

A

inhibits angiogenesis - happens in body naturally

35
Q

What will happen if you throw in TIMP3 in a population expressing VEGF? What does this indicate?

A

decreases number of vessels shown | inhibitory affect is only specific to TIMP3

36
Q

What is the correlation between VEGF and metastasis?

A

as tumor cells expressed VEGF = ability to metastasize became greater

37
Q

What was the approach Avastin was aiming to take in inhibiting VEGF?

A

use of humanized murine antibodies to bind to VEGF = neutralize them

38
Q

What is endostatin? How is it used as a chemotherapeutic drug?

A

binds to sugars and can bind to certain receptors | upon binding = freezes endothelial cells from dividing (reasons are unknown) = stops growth of blood vessels

39
Q

What is the Chick Chorioallantoic Assay?

A

used to study angiogenesis in lieu of mouse models | use teflon ring on membrane in egg = add drug within area = observe presence or absence of vasculature

40
Q

What is the benefit of using zebrafish to study the hematopoietic system?

A

they are transparent = can see the vasculature and what is going on inside

41
Q

What is an adjuvant?

A

additional supportive drug

42
Q

What is a regimen?

A

combination of drugs

43
Q

What will happen to hypoxic tumor cells without an O2 supply?

A

will undergo necrosis and die

44
Q

What is the tumor path as HIF1-a induces glycolysis cycle?

A

leads to acidosis &raquo_space;> angiogenesis and progression

Cancer Cell Biology (17 decks)

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