Angiogenesis induced by tumor necrosis factor-α is mediated by α4 integrins

Peter Vanderslice, Christy L. Munsch, Eugene Rachal, David Erichsen, Kay M. Sughrue, Ann N. Truong, James N. Wygant, Bradley W. McIntyre, Suzanne G. Eskin, Ronald Tilton, Peter J. Polverini

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Tumor necrosis factor-α (TNF-α) and fibroblast growth factor-2 (FGF-2 or bFGF) are potent stimulators of angiogenesis. TNF-α, but not FGF-2, can induce the expression of vascular cell adhesion molecule-1 (VCAM-1) on the surface of endothelial cells. The soluble form of VCAM-1 has recently been demonstrated to function as an angiogenic mediator. Here we demonstrate that monoclonal antibodies directed against VCAM-1 or its α4 integrin counter-receptor inhibited TNF-α-induced endothelial cell migration in vitro. Angiogenesis induced in vivo in rat corneas by TNF-α was inhibited by a neutralizing antibody directed against the rat α4 integrin subunit. A peptide antagonist of the α4 integrins blocked TNF-α-induced endothelial cell migration in vitro and angiogenesis in rat corneas in vivo. No inhibition by the antibodies or peptide antagonist was observed either in vitro or in vivo when FGF-2 was used as the stimulus. The peptide antagonist did not inhibit TNF-α binding to its receptor nor did it block the function of αvβ3, an integrin previously implicated in TNF-α and FGF-2 mediated angiogenesis. These results demonstrate that angiogenic processes induced by TNF-α are mediated in part by α4 integrins possibly by a mechanism involving the induction of soluble VCAM-1.

Original languageEnglish (US)
Pages (from-to)265-275
Number of pages11
JournalAngiogenesis
Volume2
Issue number3
StatePublished - 1998
Externally publishedYes

Fingerprint

Integrins
Tumor Necrosis Factor-alpha
Fibroblast Growth Factor 2
Vascular Cell Adhesion Molecule-1
Cell adhesion
Endothelial cells
Peptides
Endothelial Cells
Rats
Molecules
Cornea
Cell Movement
Antibodies
Tumor Necrosis Factor Receptors
Angiogenesis Inducing Agents
Monoclonal antibodies
Neutralizing Antibodies
Fibroblasts
Monoclonal Antibodies
In Vitro Techniques

ASJC Scopus subject areas

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

Cite this

Vanderslice, P., Munsch, C. L., Rachal, E., Erichsen, D., Sughrue, K. M., Truong, A. N., ... Polverini, P. J. (1998). Angiogenesis induced by tumor necrosis factor-α is mediated by α4 integrins. Angiogenesis, 2(3), 265-275.

Angiogenesis induced by tumor necrosis factor-α is mediated by α4 integrins. / Vanderslice, Peter; Munsch, Christy L.; Rachal, Eugene; Erichsen, David; Sughrue, Kay M.; Truong, Ann N.; Wygant, James N.; McIntyre, Bradley W.; Eskin, Suzanne G.; Tilton, Ronald; Polverini, Peter J.

In: Angiogenesis, Vol. 2, No. 3, 1998, p. 265-275.

Research output: Contribution to journalArticle

Vanderslice, P, Munsch, CL, Rachal, E, Erichsen, D, Sughrue, KM, Truong, AN, Wygant, JN, McIntyre, BW, Eskin, SG, Tilton, R & Polverini, PJ 1998, 'Angiogenesis induced by tumor necrosis factor-α is mediated by α4 integrins', Angiogenesis, vol. 2, no. 3, pp. 265-275.
Vanderslice P, Munsch CL, Rachal E, Erichsen D, Sughrue KM, Truong AN et al. Angiogenesis induced by tumor necrosis factor-α is mediated by α4 integrins. Angiogenesis. 1998;2(3):265-275.
Vanderslice, Peter ; Munsch, Christy L. ; Rachal, Eugene ; Erichsen, David ; Sughrue, Kay M. ; Truong, Ann N. ; Wygant, James N. ; McIntyre, Bradley W. ; Eskin, Suzanne G. ; Tilton, Ronald ; Polverini, Peter J. / Angiogenesis induced by tumor necrosis factor-α is mediated by α4 integrins. In: Angiogenesis. 1998 ; Vol. 2, No. 3. pp. 265-275.
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