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Therapeutic antibodies targeting angiomotin inhibit angiogenesis in vivo
Author(s) -
Levchenko Tetyana,
Veitonmaki Niina,
Lundkvist Andrea,
Gerhardt Holger,
Ming Yue,
Berggren Kristina,
Kvanta Anders,
Carlsson Roland,
Holmgren Lars
Publication year - 2008
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/fj.07-9509com
Subject(s) - angiostatin , angiogenesis , endothelial stem cell , filopodia , biology , neovascularization , cancer research , cell migration , microbiology and biotechnology , in vivo , immunology , cell , in vitro , biochemistry , actin
We have previously shown that angiomotin (Amot) mediates angiostatin inhibition of endothelial migration and tube formation in vitro . A crucial role of angiomotin in regulating endothelial cell motility is indicated by the findings that knockdown of Amot in zebrafish reduces the number of filopodia of endothe‐lial tip cells and severely impairs the migration of intersegmental vessels. In addition, targeting angiomotin using DNA vaccination inhibits angiogenesis and tumor growth in vivo . In this report’ we have generated antibodies that’ similar to angiostatin’ bind to angiomo‐tin on the endothelial cell surface. These antibodies inhibited FGF‐2 and vascular endothelial growth factor (VEGF) ‐induced endothelial migration in the Boyden chamber assay. Furthermore, the anti‐Amot B06 antibody significantly reduced the number of endothelial filopodia and inhibited vessel migration during retinal angiogenesis in vivo . We also show that systemic or local treatment with this antibody inhibits pathological blood vessel formation associated with tumor growth or laser‐induced choroid neovascularization of the eye. These findings provide a rationale for using angiomotin antibodies for specifically targeting endothelial migration in angiogenesis‐dependent diseases.—Levchenko T., Veitonmaki N., Lundkvist, A., Gerhardt, H., Ming, Y., Berggren, K., Kvanta, A., Carlsson, R., Holmgren L. Therapeutic antibodies targeting angiomotin inhibit angiogenesis in vivo . FASEB J . 22, 880–889 (2008)