F4, a collagen XIX-derived peptide, inhibits tumor angiogenesis through αvβ3 and α5β1 integrin interaction

Jean-Baptiste Oudart1,2, Matthieu Villemin1, Bertrand Brassart1

  • 1UMR CNRS/URCA 7369, Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), Université de Reims Champagne Ardenne (URCA), Reims, France.

Insights

The F4 peptide, derived from collagen XIX, inhibits melanoma cell migration and angiogenesis. It targets αvβ3 and α5β1 integrins, showing potential as an anti-cancer agent.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • F4 peptide from collagen XIX previously showed inhibition of melanoma cell migration and cancer progression.
  • The anti-angiogenic properties of F4 peptide were not previously investigated.

Purpose of the Study:

  • To investigate the anti-angiogenic properties of F4 peptide.
  • To identify the molecular targets of F4 peptide in endothelial cells.

Main Methods:

  • VEGF-induced pseudo-tube formation assay on Matrigel.
  • Rat aortic ring assay for endothelial sprouting.
  • Affinity chromatography and solid-phase assays to identify and confirm F4 peptide-integrin interactions.

Main Results:

  • F4 peptide inhibited VEGF-induced endothelial cell pseudo-tube formation and endothelial sprouting.
  • αvβ3 and α5β1 integrins were identified as potential receptors for F4 peptide.
  • Direct interaction between F4 peptide and both αvβ3 and α5β1 integrins was confirmed.

Conclusions:

  • F4 peptide exhibits potent anti-angiogenic properties.
  • F4 peptide directly interacts with αvβ3 and α5β1 integrins on endothelial cells.
  • F4 peptide is a promising antitumor agent due to its dual action on angiogenesis and tumor cell migration.

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

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...
2.9K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
3.1K
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

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...
6.1K
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
7.1K
Type IV Collagen of Basal Lamina01:05

Type IV Collagen of Basal Lamina

Type IV collagen is a 400 nm long, network-forming collagen that acts as a barrier between the epithelial and endothelial cells. Type IV collagen  forms the backbone of the basement membrane by scaffolding with laminin, entactin, proteoglycans, and fibronectin. Apart from rendering structural support to the basement membrane, it also helps entail signaling potentials necessary for both pathological and physiological functions.
A type IV collagen molecule has six alpha chains which can...
2.5K
Fibril-associated Collagen01:11

Fibril-associated Collagen

Fibril-associated collagens are a type of collagens present in the extracellular matrix with interrupted triple helices or FACIT (Fibril-associated collagens interrupted triple-helices). FACIT help connect and attach the collagen fibrils with each other as well as with other proteins of the extracellular matrix.
For example, the type II collagen fibrils in cartilage have covalently bound type IX fibril-associated collagens at regular intervals. Other types of fibril-associated collagens are...
2.8K