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Cancer Biology > Angiogenesis and EMT > Flashcards

Angiogenesis and EMT Flashcards

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1
Q

define angiogenesis

A

formation of new blood vessels

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2
Q

angiogenesis is aka

A

neovascularization

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3
Q

what proteins do cells secrete that stimulate the growth and spread of new blood vessels

A

VEGF & bFGF

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4
Q

what does VEGF stand for

A

vascular endothelial growth factor

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5
Q

what does bFGF stand for

A

basic fibroblast growth factor

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6
Q

in the experiment with a rabbit’s eye where were the tumor cells implanted that proved tumor growth was dependent on angiogenesis

A
  • anterior chamber of the eye (no growth)
  • iris of the eye (blood vessel growth & increased tumor size)
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7
Q

what was suggested after observing vessel growth when cancer cells were placed within a non-permeable membrane

A

cancer cells produced an agent that diffused through the membrane, inducing angiogenesis

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8
Q

describe the steps of VEGF triggering angiogenesis

A

cancer cells secrete VEGF -> VEGF binds to receptors on endothelial cells -> signal transduction proteins promote gene expression & cell response

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9
Q

what cell responses occur due to VEGF triggering angiogenesis

A
  1. proliferation of endothelial cells
  2. secretion of MMPs
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10
Q

what do MMPs stand for

A

matrix metalloproteinases

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11
Q

what is the function of MMPs

A
  • degrade extracellular matrix
  • contribute to metastasis
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12
Q

what are some additional functions of VEGF

A
  • formation of capillaries and lymph ducts
  • capillary permeability
  • regulation of endothelial cells
  • monocyte migration
  • hematopoiesis
  • recruitment of hematopoietic progenitor cells from bone marrow
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13
Q

what are 2 other forms of neovascularization

A
  1. vasculogenic mimicry
  2. vasculogenesis
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14
Q

define vasculogenic mimicry

A

melanoma cells form vascular-like structures

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15
Q

define vasculogenesis

A

endothelial progenitor cells differentiate and proliferate

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16
Q

most _____ consist of epithelial cancer cells and recruited ___ cells

A

carcinomas

stromal

17
Q

what do carcinomas depend on for support

A

stromal cells

18
Q

what is critical for supporting angiogenesis and metastasis

A

the extracellular matrix (ECM)

19
Q

what are critical components of the stroma

A

endothelial cells

20
Q

what do endothelial cells secrete

A

PDGF

21
Q

what do PDFGs recruit

A

pericytes which help build outer capillary walls

22
Q

what enables tumor cells to stimulate wound healing response

A

heterotypic signaling

23
Q

list the 4 stages of EMT

A
  1. loss of tight junctions
  2. cytoskeletal changes/ formation of stress fibers
  3. suppression of epithelial genes and activation of mesenchymal genes
  4. increased motility and migration
24
Q

what does EMT enable cancer cells to do

A

invade the basal layer

25
Q

what is secreted that enables degradation of ECM making space for proliferation and metastasis

A

MMPs and TGF-B

26
Q

what does MET allow

A

the reestablishment of tumors (metastasis)

27
Q

what are some examples of angiogenic factors

A
  • VEGF
  • TGF-B
  • PDGF
28
Q

what will endothelial cells stimulated by angiogenics express

A

FAS death receptor

29
Q

what is the function of thrombospondin (TSP-1)

A

releases FasL launching apoptosis

30
Q

antiangiogenics target ____________ more effectively than __________ vasculature

A
  • neovascularization
  • established
31
Q

list some examples of endogenous inhibitors of angiogenesis

A
  • endostatin
  • angiostatin
  • vasostatin
32
Q

what is the most common type of anti-angiogenic drug

A

avastin

33
Q

avastin’s activity…

A

anti-VEGF-A

34
Q

what points of the VEGF pathway are targets of therapeutic agents

A
  • ligand binding
  • VEGF receptor
  • endothelial proliferation
35
Q

explain the effects of targeting cancer w/ PDGF receptor inhibitor

A
  • pericyte protection is impaired
  • endothelial cells are sensitive to VEGF-R inhibition and chemotherapy
36
Q

what was a treatment discussed for neovascularization

A

combretastatin

37
Q

what is vascular targeting by nanotechnology

A

nanoparticles have a ligand -> mutant raf gene is internalized inhibiting the raf pathway of angiogenesis

38
Q

what are the 2 limitations of treatment of neovascularization

A
  1. tumor cells may cause necrosis
  2. tumors may return more aggressive and invasive

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