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Related Concept Videos

Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

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Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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A Comprehensive Procedure to Evaluate the In Vitro Performance of the Putative Hemangioblastoma Neovascularization Using the Spheroid Sprouting Assay
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Sprouting Angiogenesis in Human Pituitary Adenomas.

Jie Zhou1, Yaomin Hu1, Wende Zhu1

  • 1Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.

Frontiers in Oncology
|May 23, 2022
PubMed
Summary
This summary is machine-generated.

Pituitary tumors exhibit increased angiogenesis, primarily driven by placental growth factor (PGF) and vascular endothelial growth factor C (VEGF-C). Angiogenesis inhibitors show promise for treating aggressive pituitary tumors.

Keywords:
Rb1 miceVEGF inhibitorangiogenesis inhibitionangiogenic gene expressioncabozantinibendothelial markerpituitary adenomasprouting angiogenesis

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Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Angiogenesis, the formation of new blood vessels, plays a critical role in tumor growth and progression.
  • The specific mechanisms of angiogenesis in pituitary tumors are not fully elucidated, hindering the development of targeted therapies.

Purpose of the Study:

  • To investigate the role of angiogenesis in human pituitary tumors.
  • To identify key angiogenic factors involved in pituitary tumor development.
  • To evaluate the efficacy of angiogenesis inhibitors as potential therapeutic agents for aggressive pituitary tumors.

Main Methods:

  • Quantitative analysis of 71 angiogenic genes in 219 human pituitary tumors and 12 normal pituitary glands using qPCR arrays and TaqMan probes.
  • In vitro endothelial tube formation assays to assess angiogenesis inhibition.
  • In vivo studies in RbΔ19 mice to evaluate the therapeutic potential of angiogenesis inhibitors.

Main Results:

  • Pituitary tumors displayed significantly elevated expression of endothelial markers (CD31, CD34, ENG) and angiogenesis growth factors (VEGFC, PGF, ANGPT2, PDGFB, TGFB1) compared to normal pituitary tissue.
  • VEGF-C and PGF expression strongly correlated with endothelial marker expression in tumors.
  • VEGFR inhibitors demonstrated efficacy in inhibiting tumor-induced angiogenesis and prolonging survival in a mouse model.

Conclusions:

  • Human pituitary tumors exhibit enhanced sprouting angiogenesis, distinct from normal pituitary tissue.
  • Placental growth factor (PGF) and vascular endothelial growth factor C (VEGFC) are key regulators of angiogenesis in pituitary tumors.
  • Angiogenesis inhibitors, particularly VEGFR2 inhibitors like cabozantinib, warrant further investigation as potential treatments for aggressive pituitary tumors.