Tumor interstitial fluid pressure may regulate angiogenic factors in osteosarcoma

Saminathan S. Nathan, Andrew G. Huvos, Jorge E. Casas-Ganem, Rui Yang, Irina Linkov, Rebecca Sowers, Gene R. DiResta, Richard Gorlick, John H. Healey

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1520-1525
Number of pages6
JournalJournal of Orthopaedic Research
Volume26
Issue number11
DOIs
StatePublished - Nov 2008

Fingerprint

Angiogenesis Inducing Agents
Extracellular Fluid
Osteosarcoma
Vascular Endothelial Growth Factor C
Pressure
Vascular Endothelial Growth Factor A
Neoplasms
Biopsy
Cell Line
Reading
Up-Regulation
Human Umbilical Vein Endothelial Cells
Growth
Paraffin
Needles
Down-Regulation
Cell Culture Techniques
Staining and Labeling
Polymerase Chain Reaction

Keywords

  • Angiogenesis
  • Interstitial fluid pressure
  • Lymphangiogenesis
  • Osteosarcoma

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Medicine(all)

Cite this

Nathan, S. S., Huvos, A. G., Casas-Ganem, J. E., Yang, R., Linkov, I., Sowers, R., ... Healey, J. H. (2008). Tumor interstitial fluid pressure may regulate angiogenic factors in osteosarcoma. Journal of Orthopaedic Research, 26(11), 1520-1525. https://doi.org/10.1002/jor.20633

Tumor interstitial fluid pressure may regulate angiogenic factors in osteosarcoma. / Nathan, Saminathan S.; Huvos, Andrew G.; Casas-Ganem, Jorge E.; Yang, Rui; Linkov, Irina; Sowers, Rebecca; DiResta, Gene R.; Gorlick, Richard; Healey, John H.

In: Journal of Orthopaedic Research, Vol. 26, No. 11, 11.2008, p. 1520-1525.

Research output: Contribution to journalArticle

Nathan, SS, Huvos, AG, Casas-Ganem, JE, Yang, R, Linkov, I, Sowers, R, DiResta, GR, Gorlick, R & Healey, JH 2008, 'Tumor interstitial fluid pressure may regulate angiogenic factors in osteosarcoma', Journal of Orthopaedic Research, vol. 26, no. 11, pp. 1520-1525. https://doi.org/10.1002/jor.20633
Nathan, Saminathan S. ; Huvos, Andrew G. ; Casas-Ganem, Jorge E. ; Yang, Rui ; Linkov, Irina ; Sowers, Rebecca ; DiResta, Gene R. ; Gorlick, Richard ; Healey, John H. / Tumor interstitial fluid pressure may regulate angiogenic factors in osteosarcoma. In: Journal of Orthopaedic Research. 2008 ; Vol. 26, No. 11. pp. 1520-1525.
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