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Scientific article
English

Involvement of the VEGF receptor 3 in tubular morphogenesis demonstrated with a human antihuman VEGFR-3 monoclonal antibody that antagonizes receptor activation by VEGF-C

Published inJournal of cell science, vol. 117, no. 13, p. 2745-2756
Errata
  • Erratum published : Persaud K, Tille JC, Liu M, Zhu Z, Jimenez X, Pereira DS, Miao HQ, Brennan LA, Witte L, Pepper MS, Pytowski B. Correction: Involvement of the VEGF receptor 3 in tubular morphogenesis demonstrated with a human antihuman VEGFR-3 monoclonal antibody that antagonizes receptor activation by VEGF-C. J Cell Sci. 2023 Sep 1;136(17):jcs261562.
  • DOI : 10.1242/jcs.261562
  • PMID : 37675777
Publication date2004
Abstract

In this report we utilize a novel antagonist antibody to the human VEGFR-3 to elucidate the role of this receptor in in vitro tubular morphogenesis of bovine and human endothelial cells (EC cells) induced by VEGF-C. The antibody hF4-3C5 was obtained by panning a human phage display library on soluble human VEGFR-3. The binding affinity constant of hF4-3C5 significantly exceeds that of the interaction of VEGFR-3 with VEGF-C. hF4-3C5 strongly inhibits the binding of soluble VEGFR-3 to immobilized VEGF-C and abolishes the VEGF-C-mediated mitogenic response of cells that expresses a chimeric human VEGFR-3-cFMS receptor. In fluorescence experiments, hF4-3C5 reactivity is observed with human lymphatic endothelial cells (LECs) and human umbilical vein endothelial cells (HUVECs). Binding of hF4-3C5 shows that about half of bovine aortic endothelial (BAE) cells express VEGFR-3 and cells in this subpopulation are primarily responsible for the chemotactic response to the mature form of VEGF-C (VEGF-C(DeltaNDeltaC)). This response was strongly inhibited by the addition of hF4-3C5. In vitro tube formation by BAE cells induced by VEGF-C(DeltaNDeltaC) was reduced by greater than 60% by hF4-3C5 whereas the response to VEGF(165) was unaffected. Addition of hF4-3C5 together with an antagonist antibody to VEGFR-2 completely abolished the response to VEGF-C(DeltaNDeltaC). Similar results were obtained with HUVECs. Together, these findings point to a role for VEGFR-3 in vascular tubular morphogenesis and highlight the utility of hF4-3C5 as a tool for the investigation of the biology of VEGFR-3.

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Citation (ISO format)
PERSAUD, Kris et al. Involvement of the VEGF receptor 3 in tubular morphogenesis demonstrated with a human antihuman VEGFR-3 monoclonal antibody that antagonizes receptor activation by VEGF-C. In: Journal of cell science, 2004, vol. 117, n° 13, p. 2745–2756. doi: 10.1242/jcs.01138
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ISSN of the journal0021-9533
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