Document Detail


The effects of tumor-derived platelet-derived growth factor on vascular morphology and function in vivo revealed by susceptibility MRI.
MedLine Citation:
PMID:  18033683     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Platelet-derived growth factors (PDGF) play a major role in pericyte recruitment in tumor capillaries. Pericytes are required for proper vessel development, and contribute to tumor angiogenesis by promoting stabilization and maturation of newly formed vessels. To investigate the effects of pericyte coverage on tumor vessel morphology and function in vivo, tumors derived from B16 melanoma cells transfected with either control plasmid (B16/ctr) or plasmid encoding full-length PDGF-BB (B16/PDGF), the latter previously shown to have enhanced blood vessel pericyte coverage and an increased tumor growth rate, were assessed using histopathological methods, Hoechst 33342-based perfusion analyses, and two noninvasive susceptibility magnetic resonance imaging (MRI) methods. Susceptibility-contrast MRI, incorporating the use of ultrasmall superparamagnetic iron oxide particles, revealed a significant (p < 0.05) reduction in vessel size index (R(v)) of B16/PDGF tumors, and which was validated histologically by the presence of significantly smaller (p < 0.001), more punctate blood vessels identified by fluorescence microscopy of the perfusion marker Hoechst 33342. Intrinsic-susceptibility MRI was used to measure the transverse MRI relaxation rate R(2)*, sensitive to changes in endogenous paramagnetic [deoxyhaemoglobin], and used to probe for vascular maturation and function. Hypercapnia (5% CO(2)/95% air) induced a negligible Delta R(2)* response in the B16/ctr and B16/PDGF tumors. In contrast, hyperoxia (5% CO(2)/95% O(2)) induced a significantly greater R(2)* reduction in the B16/PDGF tumors (p < 0.02). Together the susceptibility MRI-derived biomarkers reveal novel pericyte-dependent changes in the morphology and function of the perfused tumor vasculature in vivo.
Authors:
Simon P Robinson; Christian Ludwig; Janna Paulsson; Arne Ostman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  122     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-02-04     Completed Date:  2008-02-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1548-56     Citation Subset:  IM    
Copyright Information:
(c) 2007 Wiley-Liss, Inc.
Affiliation:
Division of Basic Medical Sciences, St. George's, University of London, Cranmer Terrace, London, United Kingdom. Simon.Robinson@icr.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Angiogenesis Inducing Agents / metabolism*
Animals
Capillaries / pathology
Hypercapnia / metabolism
Hyperoxia / metabolism
Immunohistochemistry
Magnetic Resonance Imaging*
Male
Melanoma, Experimental / blood supply*,  metabolism
Mice
Mice, Inbred C57BL
Microscopy, Fluorescence
Neovascularization, Pathologic / metabolism*
Pericytes / metabolism*
Platelet-Derived Growth Factor / metabolism*
Time Factors
Tumor Markers, Biological / metabolism*
Chemical
Reg. No./Substance:
0/Angiogenesis Inducing Agents; 0/Platelet-Derived Growth Factor; 0/Tumor Markers, Biological; 0/platelet-derived growth factor BB

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