Selective inhibition of endothelial cell proliferation by fumagillin is, not due to differential expression of methionine aminopeptidases

Jieyi Wang*, Pingping Lou, Jack Henkin

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    94 Scopus citations


    The angiogenesis inhibitors fumagillin and TNP-470 selectively inhibit the proliferation of endothelial cells, as compared with most other cell types. The mechanism of this selective inhibition remains uncertain, although methionine aminopeptidase-2 (MetAP2) has recently been found to be a target for fumagillin or TNP-470, which inactivates MetAP2 enzyme activity through covalent modification. Primary cultures of human endothelial cells and six other non-endothelial cell types were treated with fumagillin to determine its effect on cell proliferation. Only the growth of endothelial cells was completely inhibited at low concentrations of fumagillin. MetAP1 and MetAP2 levels in these cells were investigated to determine whether differential enzyme expression plays a role in the selective action of fumagillin. Western blot analysis and RT-PCR data showed that MetAP1 and MetAP2 were both expressed in these different types of cells, thus, ruling out differential expression of MetAP1 and MetAP2 as an explanation for the cell specificity of fumagillin. Expression of MetAP2, but not of MetAP1, is regulated. Treatment of human microvascular endothelial cells (HMVEC) with fumagillin resulted in threefold increases of MetAP2 protein in the cells, while MetAP1 remained constant. Similar upregulation of MetAP2 by exposure to fumagillin was also observed in non-endothelial cells, eliminating this response as an explanation for cell specificity. Taken together, these results indicate that while MetAP2 plays a critical role in the effect of fumagillin on endothelial cell proliferation, differential endogenous expression or fumagillin-induced upregulation of methionine aminopeptidases is not responsible for this observed selective inhibition. (C) 2000 Wiley-Liss, Inc.

    Original languageEnglish (US)
    Pages (from-to)465-473
    Number of pages9
    JournalJournal of Cellular Biochemistry
    Issue number3
    StatePublished - 2000


    • Angiogenesis
    • Endothelial cells
    • Fumagillin
    • MetAP2
    • Methionine aminopeptidase
    • TNP- 470
    • p67

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology


    Dive into the research topics of 'Selective inhibition of endothelial cell proliferation by fumagillin is, not due to differential expression of methionine aminopeptidases'. Together they form a unique fingerprint.

    Cite this