Tumor Angiogenesis Flashcards

1
Q

In which 5 situations does angiogenesis occur?

A
  1. Growth and differentiation
  2. Wound repair
  3. Endometrial and placental growth
  4. Retinopathies
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2
Q

What are the 4 major stimuli of angiogenesis?

A
  1. VEGF
  2. Hypoxia
  3. PDGF
  4. Angiopoietins
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3
Q

Which stimuli is the most potent factor?

A

VEGF

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4
Q

Where does VEGF come from?

A

Endothelial cells but also many others (stromal, tumors, muscle). Pretty much any cell can produce it.

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5
Q

What makes tissue hypoxic?

A

Lack of oxygen to tissues.

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6
Q

Where does PDGF come from?

A

Mainly from platelets. To a lesser extent from monocytes/macrophages.

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7
Q

Where do angiopoietins come from?

A

Endothelial cells, kidney cells, and pericytes.

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8
Q

What does histamine do to vessels?

A

Increases vascular permeability and vasodilates.

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9
Q

How does histamine induce vascular permeability?

A

Breaks adhesion junctions b/t endothelial cells.

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10
Q

Are angiogenic signals present in new capillary formation?

A

Yes.

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11
Q

List the steps of new capillary formation (5).

A
  1. Endothelial cells degrade the vascular basement membrane
  2. Endothelial cells migrate, forming tip cells, that migrate toward the stimulus
  3. Endothelial cell proliferation forms a lumen
  4. The lumen extends towards the angiogenic signals through endothelial cell division and tip cell migration
  5. Two “sprouts” fuse their lumens, providing a route for blood flow
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12
Q

How do endothelial cells degrade the vascular basement membrane?

A

They release metalloproteinases.

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13
Q

Can endothelial cells invade intact basement membranes?

A

No.

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14
Q

What is notch signaling?

A

When tip cells migrate first, they then recruit stock cells.

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15
Q

The lumen formed by endothelial cell proliferation is also called what?

A

Folkman’s sprout.

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16
Q

Arteriogenesis can alleviate what?

A

An occluded major artery.

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17
Q

In arteriogenesis, are major arterioles recruited?

18
Q

Signifcant vascular remodeling does what in arteriogenesis?

A

Thickens vascular walls and increases luminal diameter.

19
Q

How is thickening of vascular walls accomplished?

A

MCP-1 recruits macrophages. Macrophages secrete growth factors which cause endothelial cells and smooth muscle cells to grow (1 layer of endothelium and 2-3 layers of smooth muscle).

20
Q

Is arteriogenesis flow mediated?

A

Yes: pressure changes and shear stress response stimulate it.

21
Q

What is arteriogenesis?

A

The expansion of the existing arterial system.

22
Q

T or F. Arteriogenesis and angiogenesis both require the same growth factors and development of lumens.

23
Q

How does angiogenesis differ from arteriogenesis?

A

The presence of mural cells in angiogenesis. Mural cells are only present on capillaries and not on arteries.

24
Q

Where do heparin and heparan sulfates come from?

A

Mast cells.

25
What do heparin and heparan sulfates have a high affinity for?
Growth factors.
26
What cell does the binding of PDGF and heparin recruit?
Monocytes.
27
What do angiopoietins do?
Stabilize the process of angiogenesis.
28
What factors stimulate existing endothelial cells?
Proangiogenic factors.
29
Remodeling and growth results in what?
New capillaries.
30
Why must new capillaries recruite pericytes?
To provide protection and stability b/c new capillaries lack smooth muscle cells and are very fragile.
31
Does vascular maturation have to take place in angiogenesis?
Yes.
32
Why does cancer growth depend on angiogenesis?
Cancer cells require oxygen and nutrients.
33
T or F. Inhibiton of angiogenesis inhibits tumor growth but only temporarily.
T.
34
What 2 properties of tumor cells support angiogenesis?
1. Ability to produce growth factors that stimulate endothelial cells in existing capillaries 2. Tumor cells can differentiate into endothelial cells (molecular mimicry)
35
Why are some cancers refractive to anti-VEGF treatment?
Because cells in the neovasculature are mimcs that are not as responsive to VEGF. Tumor cells may exploit other pathways to induce angiogenesis.
36
T or F. Growing tumors will always need a blood supply and will therefore always be undergoing angiogenesis and requiring growth factors.
T.
37
Why is combined anti-VEGF and chemotherapy more effective than monotherapy?
Decreased interstitial pressure allows chemotherapeutic agents access to tumor cells. Otherwise, leakiness leads to diffusion of chemotherapeutic agents. Must normalize the vasculature for proper functioning of agents.
38
What are the 3 current targets of combination therapy development?
1. Anti-angiogenesis 2. Chemotherapeutic agents 3. Anti-lymphangiogenesis
39
What is the goal of anti-angiogenesis therapy?
To starve the tumor and avoid intravasation of metastatic cells.
40
Why is chemotherapy more effective in combination therapy?
Decreased interstitial pressure allows the chemotherapy more access to the tumor.
41
What is the role of anti-lymphangiogenesis therapy in combination therapy?
To maintain chemotherapeutic agent levels and prevent metastases.