Tumor interstitial fluid pressure may regulate angiogenic factors in osteosarcoma Journal Article

  


Authors: Nathan, S. S.; Huvos, A. G.; Casas Ganem, J. E.; Yang, R.; Linkov, I.; Sowers, R.; DiResta, G. R.; Gorlick, R.; Healey, J. H.
Article Title: Tumor interstitial fluid pressure may regulate angiogenic factors in osteosarcoma
Abstract: 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. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
Keywords: immunohistochemistry; osteosarcoma; adolescent; clinical article; controlled study; human tissue; bone neoplasms; bone tumor; human cell; genetics; cancer growth; cancer diagnosis; polymerase chain reaction; biological marker; biological markers; metabolism; image analysis; tumor biopsy; cancer cell culture; pathology; chemosensitivity; cell line, tumor; angiogenesis; neovascularization, pathologic; vascularization; physiology; vasculotropin c; lymphangiogenesis; vascular endothelial growth factor c; gene expression regulation; fluorescent antibody technique; gene expression regulation, neoplastic; vascular endothelium; endothelium, vascular; tumor cell line; vasculotropin a; fluorescent antibody technique, direct; down regulation; upregulation; microcirculation; image processing, computer-assisted; image processing; blood flow; extracellular fluid; tissue pressure; neovascularization (pathology); cd31 antigen; paraffin; capillary density; angiogenic factor; hypothesis; digital imaging; hydrostatic pressure; interstitial fluid pressure
Journal Title: Journal of Orthopaedic Research
Volume: 26
Issue: 11
ISSN: 0736-0266
Publisher: John Wiley & Sons  
Date Published: 2008-11-01
Start Page: 1520
End Page: 1525
Language: English
DOI: 10.1002/jor.20633
PUBMED: 18473395
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-55449116226&partnerID=40&md5=a4d4f0251e3598e76bed23b23098dbf7
Notes: --- - "Cited By (since 1996): 9" - "Export Date: 17 November 2011" - "CODEN: JORED" - "Source: Scopus"
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MSK Authors
  1. Jorge Casas-Ganem
    13 Casas-Ganem
  2. Gene Di Resta
    48 Di Resta
  3. John H Healey
    550 Healey
  4. Irina Linkov
    74 Linkov
  5. Andrew G Huvos
    289 Huvos
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