Heterophilic interactions between cell adhesion molecule L1 and αvβ3-integrin induce HUVEC process extension in vitro and angiogenesis in vivo

Heike Hall, Valentin Djonov, Martin Ehrbar, Matthias Hoechli, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Cell adhesion molecule L1 was implicated in angiogenic processes, tumor formation and metastasis. Here, we provide evidence that the sixth Ig-like domain of L1 (L1Ig6) interacts with αvβ3 to induce process extension of human umbilical vein endothelial cells (HUVECs) in vitro and angiogenesis in vivo. HUVECs formed network-like structures on full-length L1 or L1Ig6 substrates comparable to structures found on matrigel. In the presence of mab αvβ3 or cyclic RGD, apoptosis was induced. In fibrin matrices where L1Ig6 was covalently incorporated, HUVECs formed multicellular and hollow processes through interactions between cell-surface αvβ3 and RGD-sites of matrix-immobilized L1Ig6. No such processes were induced by L1Ig6 having non-functional RDG-sites, or in the presence of mab α vβ3 or cyclic RGD. In those matrices, increased apoptosis was found. Co-immunoprecipitation of L1 or L1Ig6 with αvβ3 suggests close interactions. Furthermore, L1Ig6 stimulated HUVECs showed increased tyrosine phosphorylation of αvβ3 and phosphorylation of MAP kinases (ERK1 and ERK2) but not AKT indicating specific activation of α vβ3 followed by activation of downstream kinases. Application of L1Ig6-modified fibrin matrices on CAMs induced 50-60% increased αv and αvβ3 protein expression and in vivo angiogenesis indicated by ∼50% increased mean vascular length density. The results demonstrate angiogenic potential of L1Ig6 involving ligation and activation of αvβ3.

Original languageEnglish
Pages (from-to)213-223
Number of pages11
JournalAngiogenesis
Volume7
Issue number3
DOIs
StatePublished - Sep 1 2004
Externally publishedYes

Fingerprint

Neural Cell Adhesion Molecule L1
Cell adhesion
Endothelial cells
Human Umbilical Vein Endothelial Cells
Integrins
Phosphorylation
Molecules
Chemical activation
Cell death
Fibrin
Apoptosis
Mitogen-Activated Protein Kinase 3
Computer aided manufacturing
Immunoprecipitation
Cell Communication
Ligation
Blood Vessels
Tyrosine
Tumors
Phosphotransferases

Keywords

  • αβ integrin
  • Angiogenesis
  • CAM-assay
  • Fibrin
  • HUVECS
  • L1Ig6

ASJC Scopus subject areas

  • Cancer Research
  • Pathology and Forensic Medicine
  • Clinical Biochemistry
  • Polymers and Plastics

Cite this

Heterophilic interactions between cell adhesion molecule L1 and αvβ3-integrin induce HUVEC process extension in vitro and angiogenesis in vivo. / Hall, Heike; Djonov, Valentin; Ehrbar, Martin; Hoechli, Matthias; Hubbell, Jeffrey A.

In: Angiogenesis, Vol. 7, No. 3, 01.09.2004, p. 213-223.

Research output: Contribution to journalArticle

Hall, Heike ; Djonov, Valentin ; Ehrbar, Martin ; Hoechli, Matthias ; Hubbell, Jeffrey A. / Heterophilic interactions between cell adhesion molecule L1 and αvβ3-integrin induce HUVEC process extension in vitro and angiogenesis in vivo. In: Angiogenesis. 2004 ; Vol. 7, No. 3. pp. 213-223.
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