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Title: X-ray fluorescent microscopy reveals large-scale relocalization and extracellular translocation of cellular copper during angiogenesis.

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.

Authors:
; ; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
962544
Report Number(s):
ANL/BIO/JA-57935
Journal ID: ISSN 0027-8424; PNASA6; TRN: US0902883
DOE Contract Number:
DE-AC02-06CH11357
Resource Type:
Journal Article
Resource Relation:
Journal Name: Proc. Natl. Acad. Sci. U.S.A.; Journal Volume: 104; Journal Issue: 7 ; Feb. 13, 2007
Country of Publication:
United States
Language:
ENGLISH
Subject:
43 PARTICLE ACCELERATORS; ABLATION; CARCINOMAS; CELL MEMBRANES; COMPARTMENTS; COPPER; FLUORESCENCE; IN VITRO; METALLOPROTEINS; MICROSCOPY; OPTICS; PROTEINS; SENSITIVITY; SYNCHROTRONS; TRANSLOCATION

Citation Formats

Finney, L., Mandava, S., Ursos, L., Zhang, W., Rodi, D., Vogt, S., Legnini, D., Maser, J., Ikpatt, F., Olopade, O. I., Glesne, D., and Univ. of Chicago. X-ray fluorescent microscopy reveals large-scale relocalization and extracellular translocation of cellular copper during angiogenesis.. United States: N. p., 2007. Web. doi:10.1073/pnas.0607238104.
Finney, L., Mandava, S., Ursos, L., Zhang, W., Rodi, D., Vogt, S., Legnini, D., Maser, J., Ikpatt, F., Olopade, O. I., Glesne, D., & Univ. of Chicago. X-ray fluorescent microscopy reveals large-scale relocalization and extracellular translocation of cellular copper during angiogenesis.. United States. doi:10.1073/pnas.0607238104.
Finney, L., Mandava, S., Ursos, L., Zhang, W., Rodi, D., Vogt, S., Legnini, D., Maser, J., Ikpatt, F., Olopade, O. I., Glesne, D., and Univ. of Chicago. Tue . "X-ray fluorescent microscopy reveals large-scale relocalization and extracellular translocation of cellular copper during angiogenesis.". United States. doi:10.1073/pnas.0607238104.
@article{osti_962544,
title = {X-ray fluorescent microscopy reveals large-scale relocalization and extracellular translocation of cellular copper during angiogenesis.},
author = {Finney, L. and Mandava, S. and Ursos, L. and Zhang, W. and Rodi, D. and Vogt, S. and Legnini, D. and Maser, J. and Ikpatt, F. and Olopade, O. I. and Glesne, D. and Univ. of Chicago},
abstractNote = {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.},
doi = {10.1073/pnas.0607238104},
journal = {Proc. Natl. Acad. Sci. U.S.A.},
number = 7 ; Feb. 13, 2007,
volume = 104,
place = {United States},
year = {Tue Feb 13 00:00:00 EST 2007},
month = {Tue Feb 13 00:00:00 EST 2007}
}