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TDX, a galectin‐1 and galectin‐3‐specific inhibitor, mitigates VEGF‐A‐induced angiogenesis
Author(s) -
Chen WeiSheng,
Leffler Hakon,
Nilsson Ulf J,
Panjwani Noorjahan
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.828.1
Subject(s) - angiogenesis , galectin 3 , galectin , neovascularization , corneal neovascularization , umbilical vein , cancer research , metastasis , galectin 1 , vascular endothelial growth factor , sprouting angiogenesis , chemistry , microbiology and biotechnology , cancer , medicine , biology , immunology , in vitro , vegf receptors , biochemistry
Both galectin‐1 (Gal‐1) and galectin‐3 (Gal‐3) are vital modulators for vascular endothelial growth factors receptor‐2 (VEGFR‐2) signaling pathway. To date, TDX is the only compound that specifically targets both galectins with high affinity. Our goal is to study TDX's efficacy against VEGF‐A‐mediated pathological angiogenesis. Here we showed that Gal‐1 and Gal‐3 interact with VEGFR‐2 in a carbohydrate‐dependent manner and that TDX: (i) reduces cautery‐induced corneal neovascularization in vivo, (ii) reduces VEGF‐A‐induced sprouting of human umbilical vein endothelial cells (HUVECs) as assessed by a three‐dimensional sprouting assay, (iii) efficiently abolishes VEGF‐A‐induced HUVEC chemotaxis, (iv) has little effect on HUVEC viability, and (v) does not affect total protein expression of VEGFR‐2 in HUVECs. Our data provide proof of principle that targeting Gal‐1 and Gal‐3 by the novel, small molecule inhibitor, TDX, ameliorates pathological angiogenesis. The findings provide a new therapeutic strategy for various disease conditions, including inflammation, diabetes, cancer metastasis, age‐related macular degeneration and corneal neovascularization. This work is supported by the NIH Grant R01EY007088 to N. Panjwani.