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CMBM Exam 4 > Angiogenesis > Flashcards

Angiogenesis Flashcards

1
Q

Hemangioblast

A
  • Link hematopoietic and vascular systems during embryonic development producing hematopoietic stem cells and angioblasts
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2
Q

Angioblasts

A
  • Endothelial cell precursors in vasculogenesis
  • Proliferate and migrate to peripheral sites and differentiate into endothelial cells that form arteries, veins and lymphatics, pericytes and smooth muscle cells
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3
Q

Angioblast like cells

A
  • Stored in adult bone marrow
  • Recruited to tissue to initiate angiogenesis
  • Express markers for hematopoietic stem cells and endothelial specific markers
  • Participate in replacement of lost endothelial cells, reendothelization of vascular implants, cutaneous wounds and tumors
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4
Q

VEGF

A
  • At the center of the angiogenic pathway
  • Increases vascular permeability during angiogenesis
  • Secreted by mesenchymal and stromal cells
  • Stimulates vascular endothelial cell growth, survival and proliferation
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5
Q

FGF-2

A
  • Enhances endothelial proliferation, differentiation and migration towards angiocentric stimulus
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6
Q

Angiopoietins 1 and 2, PDGF, TGF beta

A
  • Participate in blood vessel stabilization
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7
Q

Ang 1

A
  • Interacts w/receptor on endothelial cells called Tie 2 to recruit periendothelial cells
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8
Q

PDGF

A
  • Recruits smooth muscle cells
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9
Q

TGF beta

A
  • Stabilized newly formed vessels
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10
Q

Ang1/Tie2

A
  • Mediates vessel maturation and maintains endothelial quiescence; meaning its going to dampen down the proliferative process
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11
Q

Ang2/Tie2

A
  • Loosens endothelial cells making them more responsive to VEGF and inhibitors of angiogenesis
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12
Q

Form and maintains new blood vessels

A
  • Integrin
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13
Q

Matricellular proteins

A
  • Destabilize cell matrix interactions and promote angiogenesis
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14
Q

Proteinases

A
  • Plasminogen activator and metalloproteinases remodel tissues during endothelial invasion, also release VEGF, FGF-2
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15
Q

Newly formed endothelial cells stimulate the growth of adjacent tumor cells by secreting

A
  • Growth factors and PDGF
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16
Q

Tumor vessels irregularly shaped and lead due to increased levels of

A
  • VEGF
17
Q

Tumors often have high levels of

A
  • VEGF and FGF
18
Q

“Angiogenic Switch” regulators

A
  • Activators: VEGF, FGF, IL-8
  • Inhibitors: thrombospondin-1, angiostatin, interferon-alpha/beta)
19
Q

Environment and cellular triggers that induce VEGF pathway

A
  • Hypoxia

*gene expression of VEGF is upregulated in response to hypoxic conditions

  • Oncogenes

*oncogenes and tumor suppressor genes are assoc. w/increased VEGF production

  • Cellular receptors

*EGFR, HER-2, IGF-1R activation or overexpression

  • Other growth factors and cytokines

*COX-2, PDGF

20
Q

VEGF-1

A
  • Crucial to embryonic angiogenesis
  • Does not appear to be critical in pathogenic angiogenesis
21
Q

VEGFR-2

A
  • Tyrosine kinase receptor present on endothelial cells and their precursors

*expressed on tumor cells as well

  • Mediates proliferation, migration, survival and angiogenesis
  • VEGF and VEGFR-2 stimulate endothelial cell precursors from bone marrow, increase proliferation of the cells at site of angiogenesis
  • Most important VEGF receptor in tumor angiogenesis
  • Mediates the majority of VEGF angiogenic effects
22
Q

VEGFR-3

A
  • Found only in lymphatic endothelial cells
  • Assoc. w/lymph node metastasis
  • Effects mainly in lymphatic cells
23
Q

VEGF and cancer

A
  • Increases interstitial pressure

*high interstital pressure may imped delivery of therapeutic agents to tumors

  • May prevent immune response to tumors
  • Continuously expressed throughout the entire tumor life cycle
  • Direct and continuous VEFG inhibition is an important antitumor strategy
  • Potent and predominant factor in metastasis of tumors
  • Can prevent functional maturation of dendritic cells
  • VEGF overexpression has been assoc. w/poor prognosis in a variety of solid tumor types

CMBM Exam 4 (14 decks)

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