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J. Biol. Chem., Vol. 277, Issue 49, 47626-47635, December 6, 2002
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From the We have carried out a comprehensive molecular
mapping of PG-M/versican isoforms V0-V3 in adult human tissues and
have specifically investigated how the expression of these isoforms is
regulated in endothelial cells in vitro. A survey of 21 representative tissues highlighted a prevalence of V1 mRNA;
demonstrated that the relative frequency of expression was V1 > V2 > V3
Distribution of PG-M/Versican Variants in Human Tissues and
de Novo Expression of Isoform V3 upon Endothelial Cell
Activation, Migration, and Neoangiogenesis in Vitro*
§¶,
,§
Department of Evolutionary and Functional
Biology, University of Parma, Viale delle Scienze 11/A,
43100 Parma, Italy, § Division for Experimental Oncology 2, National Cancer Institute, Centro di Riferimento Oncologico-Instituto
di Ricerca e Cura a Carattere Scientifico, Via Pedemontana Occidentale
12, Aviano (PN) 33081 Italy, Department for Cell and Molecular
Biology, University of Lund, Box 94, S-22100 Lund, Sweden, and
** Department of Technical and Biomedical Sciences & the
Microgravity, Aging, Training, and Immobility Centre of Excellence,
University of Udine, Piazzale Kolbe Udine, 35100 Italy
V2; and showed that <15% of the tissues
transcribed significant levels of all four isoforms. By employing novel
and previously described anti-versican antibodies we verified a
ubiquitous versican deposition in normal and tumor-associated vascular
structures and disclosed differences in the glycanation profiles of
versicans produced in different vascular beds. Resting endothelial
cells isolated from different tissue sources transcribed several of the
versican isoforms but consistently failed to translate these mRNAs
into detectable proteoglycans. However, if stimulated with tumor
necrosis factor-
or vascular endothelial growth factor,
they altered their versican expression by de novo
transcribing the V3 isoform and by exhibiting a moderate V1/V2
production. Induced versican synthesis and de novo V3
expression was also observed in endothelial cells elicited to migrate
in a wound-healing model in vitro and in angiogenic
endothelial cells forming tubule-like structures in Matrigel or fibrin
clots. The results suggest that, independent of the degree of
vascularization, human adult tissues show a limited expression of
versican isoforms V0, V2, and V3 and that endothelial cells may
contribute to the deposition of versican in vascular structures, but
only following proper stimulation.
*
This work was supported by grants from the Italian Ministry
of Health (FSN RF99 and RF00), Associazione Italiana Ricerca sul Cancro
(AIRC), and intramural research funds provided by the University of
Parma.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.:
39-0521-906601; Fax: 39-0521-905657; E-mail: rperris@cro.it.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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