Tetraiodothyroacetic acid, a small molecule integrin ligand, blocks angiogenesis induced by vascular endothelial growth factor and basic fibroblast growth factor

Shaker A. Mousa, Joel J. Bergh, Emie Dier, Abdelhadi Rebbaa, Laura J. O'Connor, Murat Yalcin, Ahmad Aljada, Evgeny Dyskin, Faith B. Davis, Hung Yung Lin, Paul J. Davis

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81 Citations (Scopus)

Abstract

Thyroid hormone has been recently shown to induce tumor growth and angiogenesis via a plasma-membrane hormone receptor on integrin αVβ3. The receptor is at or near the Arg-Gly-Asp (RGD) recognition site on the integrin that is important to extracellular matrix (ECM) protein and vascular growth factor interactions with the integrin. In the present study, we examined the possibility that tetraiodothyroacetic acid (tetrac), a deaminated, non-agonist thyroid hormone analog that binds to the integrin receptor, may modulate vascular growth factor-induced angiogenesis in the absence of thyroid hormone. Angiogenesis models were studied in which VEGF or FGF2 (1-2 μg/ml) induced tube formation in human dermal microvascular endothelial cells (HDMEC), stimulated new blood vessel branch formation in the chick chorioallantoic membrane (CAM) and induced angiogenesis in the mouse matrigel model. In all models, tetrac (1-10 μM) and at 10 μg in mouse matrigel inhibited the pro-angiogenesis activity of VEGF and FGF2 by more than 50%. RT-PCR revealed that tetrac (1-3 μM) decreased abundance of angiopoietin-2 mRNA, but not angiopoietin-1 mRNA, in VEGF-exposed endothelial cells, suggesting that specific angiogenic pathways are targeted by tetrac. Tetrac is a novel, inexpensive small molecule whose anti-angiogenic activity in the present studies is proposed to reflect inhibition, via the integrin RGD recognition/thyroid hormone receptor site, of crosstalk between plasma-membrane vascular growth factor receptors and integrin αVβ3.

Original languageEnglish
Pages (from-to)183-190
Number of pages8
JournalAngiogenesis
Volume11
Issue number2
DOIs
Publication statusPublished - Jun 2008
Externally publishedYes

Keywords

  • Angiogenesis
  • Growth factors
  • Integrin
  • Tetrac
  • Thyroid hormone

ASJC Scopus subject areas

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

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    Mousa, S. A., Bergh, J. J., Dier, E., Rebbaa, A., O'Connor, L. J., Yalcin, M., Aljada, A., Dyskin, E., Davis, F. B., Lin, H. Y., & Davis, P. J. (2008). Tetraiodothyroacetic acid, a small molecule integrin ligand, blocks angiogenesis induced by vascular endothelial growth factor and basic fibroblast growth factor. Angiogenesis, 11(2), 183-190. https://doi.org/10.1007/s10456-007-9088-7