A naturally occurring soluble form of vascular endothelial growth factor receptor 2 detected in mouse and human plasma

John M L Ebos, Guido Bocci, Shan Man, Philip E. Thorpe, Daniel J. Hicklin, Danielle Zhou, Xiaohong Jia, Robert S. Kerbel

Research output: Contribution to journalArticle

154 Scopus citations

Abstract

Angiogenesis and vasculogenesis are regulated in large part by several different growth factors and their associated receptor tyrosine kinases (RTKs). Foremost among these is the vascular endothelial growth factor (VEGF) family including VEGF receptor (VEGFR)-2 and -1. VEGFR ligand binding and biological activity are regulated at many levels, one of which is by a soluble, circulating form of VEGFR-1 (sVEGFR-1). This sVEGFR-1 can act as a competitive inhibitor of its ligand, serve as a possible biomarker, and play important roles in cancer and other diseases such as preeclampsia. Recombinant forms of sVEGFR-2 have been shown to have antiangiogenic activity, but a naturally occurring sVEGFR-2 has not been described previously. Here, we report such an entity. Having a molecular weight of ∼160 kDa, sVEGFR-2 can be detected in mouse and human plasma with several different monoclonal and polyclonal anti-VEGFR-2 antibodies using both ELISA and immunoprecipitation techniques. In vitro studies have determined that the sVEGFR-2 fragment can be found in the conditioned media of mouse and human endothelial cells, thus suggesting that it may be secreted, similar to sVEGFR-1, or proteolytically cleaved from the cell. Potential biological activity of this protein was inferred from experiments in which mouse sVEGFR-2 could bind to VEGF-coated plates. Similar to sVEGFR-1 and other soluble circulating RTKs, sVEGFR-2 may have regulatory consequences with respect to VEGF-mediated angiogenesis as well as potential to serve as a quantitative biomarker of angiogenesis and antiangiogenic drug activity, particularly for drugs that target VEGF or VEGFR-2.

Original languageEnglish (US)
Pages (from-to)315-326
Number of pages12
JournalMolecular Cancer Research
Volume2
Issue number6
StatePublished - Jun 1 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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    Ebos, J. M. L., Bocci, G., Man, S., Thorpe, P. E., Hicklin, D. J., Zhou, D., Jia, X., & Kerbel, R. S. (2004). A naturally occurring soluble form of vascular endothelial growth factor receptor 2 detected in mouse and human plasma. Molecular Cancer Research, 2(6), 315-326.