The α4 laminin subunit regulates endothelial cell survival

K. C. DeHahn, M. Gonzales, A. M. Gonzalez, S. B. Hopkinson, N. S. Chandel, J. K. Brunelle, J. C.R. Jones*

*Corresponding author for this work

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

The α4 laminin subunit is a major structural component of assembling basement membranes of endothelial cells. We have been investigating its functions with regard to endothelial cell survival. An anti-laminin α4 antibody (2A3), directed against the G domain of the α4 laminin subunit of laminins-8 and -9, inhibits proliferation and enhances apoptosis of endothelial cells when cells are maintained in vitro. Activation of caspases-9 and -3 plays a role in 2A3 antibody-induced apoptosis, since inhibitors specific for these caspases and overexpression of the anti-apoptotic protein Bcl-XL, but not c-FLIP, inhibit 2A3 antibody-triggered endothelial cell death. Extracellular matrix is known to play a role in regulating programmed cell death in an integrin-dependent fashion. The α4 laminin subunit conforms to this idea since activation of β1 integrin subunits on endothelial cells blocks the ability of 2A3 antibody to induce endothelial cell death. In summary, our data indicate that complexes composed of α4 laminin/β1 subunit-containing integrins at the cell surface support endothelial cell survival. Furthermore, we propose that antagonists of α4 laminin function, including antibody 2A3, have value as angiogenesis inhibitors in a clinical setting where blocking aberrant growth of blood vessel by triggering apoptosis of endothelial cells may be therapeutic.

Original languageEnglish (US)
Pages (from-to)281-289
Number of pages9
JournalExperimental Cell Research
Volume294
Issue number1
DOIs
StatePublished - Mar 10 2004

Keywords

  • Angiogenesis
  • Caspase
  • Extracellular matrix
  • Integrin
  • Laminin
  • Programmed cell death

ASJC Scopus subject areas

  • Cell Biology

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