X-ray flourescence microscopy reveals large-scale relocalization and extracellular translocation of cellular copper during angiogenesis

Lydia Finney, Suneeta Mandava, Lyann Ursos, Wen Zhang, Diane Rodi, Stefan Vogt, Daniel Legnini, Jorg Maser, Francis Ikpatt, Olyfunmilayo I. Olopade, David Glesne

Research output: Contribution to journalArticle

132 Scopus citations

Abstract

Although copper has been reported to influence numerous proteins known to be important for angiogenesis, the enhanced sensitivity of this developmental process to copper bioavailability has remained an enigma, because copper metalloproteins are prevalent and essential throughout all cells. Recent developments in x-ray optics at third-generation synchrotron sources have provided a resource for highly sensitive visualization and quantitation of metalloproteins in biological samples. Here, we report the application of x-ray fluorescence microscopy (XFM) to in vitro models of angiogenesis and neurogenesis, revealing a surprisingly dramatic spatial relocalization specific to capillary formation of 80-90% of endogenous cellular copper stores from intracellular compartments to the tips of nascent endothelial cell filopodia and across the cell membrane. Although copper chelation had no effect on process formation, an almost complete ablation of network formation was observed. XFM of highly vascularized ductal carcinomas showed copper clustering in putative neoangiogenic areas. This use of XFM for the study of a dynamic developmental process not only sheds light on the copper requirement for endothelial tube formation but highlights the value of synchrotron-based facilities in biological research.

Original languageEnglish (US)
Pages (from-to)2247-2252
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number7
DOIs
StatePublished - Feb 13 2007

Keywords

  • Copper chelation
  • Human microvascular endothelial cells
  • Infiltrating ductal breast carcinoma

ASJC Scopus subject areas

  • General

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