Tumour 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

6 Citations (Scopus)

Abstract

Purpose: We have previously shown that osteosarcomas 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 osteosarcomas regulates angiogenesis. Materials and Methods: Sixteen patients with the clinical diagnosis of osteosarcomas 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 paraffi n-embedded tissue blocks of the biopsy samples. Clinical results were validated in a pressurised cell culture system. Results: IFPs in the tumours (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 tumours compared to high vascularity tumours (P <0.001). In the osteosarcoma cell lines, growth in a pressurised environment was associated with VEGF-A downregulation, VEGF-C upregulation and TPA upregulation. The reverse was seen in the OB cell lines. Growth in the HUVEC cell line was not significantly inhibited in a pressurised 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. Conclusion: Our data suggest that some molecules in angiogenesis are regulated by changes in IFP.

Original languageEnglish (US)
Pages (from-to)1041-1047
Number of pages7
JournalAnnals of the Academy of Medicine Singapore
Volume38
Issue number12
StatePublished - Dec 2009

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
Needles
Down-Regulation
Cell Culture Techniques
Staining and Labeling
Polymerase Chain Reaction

Keywords

  • Angiogenesis
  • Lymphangiogenesis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Nathan, S. S., Huvos, A. G., Casas-Ganem, J. E., Yang, R., Linkov, I., Sowers, R., ... Healey, J. H. (2009). Tumour interstitial fluid pressure may regulate angiogenic factors in osteosarcoma. Annals of the Academy of Medicine Singapore, 38(12), 1041-1047.

Tumour 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: Annals of the Academy of Medicine Singapore, Vol. 38, No. 12, 12.2009, p. 1041-1047.

Research output: Contribution to journalArticle

Nathan, SS, Huvos, AG, Casas-Ganem, JE, Yang, R, Linkov, I, Sowers, R, DiResta, GR, Gorlick, R & Healey, JH 2009, 'Tumour interstitial fluid pressure may regulate angiogenic factors in osteosarcoma', Annals of the Academy of Medicine Singapore, vol. 38, no. 12, pp. 1041-1047.
Nathan SS, Huvos AG, Casas-Ganem JE, Yang R, Linkov I, Sowers R et al. Tumour interstitial fluid pressure may regulate angiogenic factors in osteosarcoma. Annals of the Academy of Medicine Singapore. 2009 Dec;38(12):1041-1047.
Nathan, Saminathan S. ; Huvos, Andrew G. ; Casas-Ganem, Jorge E. ; Yang, Rui ; Linkov, Irina ; Sowers, Rebecca ; DiResta, Gene R. ; Gorlick, Richard ; Healey, John H. / Tumour interstitial fluid pressure may regulate angiogenic factors in osteosarcoma. In: Annals of the Academy of Medicine Singapore. 2009 ; Vol. 38, No. 12. pp. 1041-1047.
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