Document Detail

Tumor interstitial fluid pressure may regulate angiogenic factors in osteosarcoma.
MedLine Citation:
PMID:  18473395     Owner:  NLM     Status:  MEDLINE    
We have previously shown that osteosarcomas (OS) have states of increased interstitial fluid pressure (IFP), which correlate with increased proliferation and chemosensitivity. In this study, we hypothesized that constitutively raised IFP in OS regulates angiogenesis. Sixteen patients with the clinical diagnosis of OS underwent blood flow and IFP readings by the wick-in-needle method at the time and location of open biopsy. Vascularity was determined by capillary density in the biopsy specimens. We performed digital image analysis of immunohistochemical staining for CD31, VEGF-A, VEGF-C, and TPA on paraffin-embedded tissue blocks of the biopsy samples. Clinical results were validated in a pressurized cell culture system. Interstitial fluid pressures in the tumors (mean 33.5 +/- SD 17.2 mmHg) were significantly higher (p = 0.00001) than that in normal tissue (2.9 +/- 5.7 mmHg). Pressure readings were significantly higher in low vascularity tumors compared to high vascularity tumors (p < 0.001). In the OS cell lines, growth in a pressurized environment was associated with VEGF-A downregulation, VEGF-C upregulation, and TPA upregulation. The reverse was seen in the OB cell line. Growth in the HUVEC cell line was not significantly inhibited in a pressurized environment. Immunohistochemical assessment for VEGF-A (p = 0.01), VEGF-C (p = 0.008), and TPA (p = 0.0001) translation were consistent with the findings on PCR. Our data suggests that some molecules in angiogenesis are regulated by changes in IFP.
Saminathan S Nathan; Andrew G Huvos; Jorge E Casas-Ganem; Rui Yang; Irina Linkov; Rebecca Sowers; Gene R DiResta; Richard Gorlick; John H Healey
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of orthopaedic research : official publication of the Orthopaedic Research Society     Volume:  26     ISSN:  1554-527X     ISO Abbreviation:  J. Orthop. Res.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-10-22     Completed Date:  2008-11-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8404726     Medline TA:  J Orthop Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1520-5     Citation Subset:  IM    
Copyright Information:
(c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
Musculoskeletal Oncology Service, Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 5, Lower Kent Ridge Road, Singapore 119074, Singapore.
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MeSH Terms
Biological Markers / metabolism
Bone Neoplasms / blood supply*,  metabolism,  pathology
Cell Line, Tumor
Endothelium, Vascular / metabolism
Extracellular Fluid / metabolism*
Fluorescent Antibody Technique, Direct
Gene Expression Regulation, Neoplastic
Hydrostatic Pressure
Image Processing, Computer-Assisted
Lymphangiogenesis / physiology
Microcirculation / metabolism,  pathology
Neovascularization, Pathologic / metabolism*
Osteosarcoma / blood supply*,  metabolism,  pathology
Vascular Endothelial Growth Factor C / genetics,  metabolism*
Reg. No./Substance:
0/Biological Markers; 0/Vascular Endothelial Growth Factor C

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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