Tumour 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: | Tumour interstitial fluid pressure may regulate angiogenic factors in osteosarcoma |
| 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. |
| Keywords: | immunohistochemistry; osteosarcoma; adolescent; clinical article; controlled study; bone neoplasms; human cell; conference paper; polymerase chain reaction; cells, cultured; image analysis; angiogenesis; neovascularization, pathologic; vascularization; vasculotropin c; lymphangiogenesis; cell culture; vasculotropin a; down regulation; upregulation; blood flow; pressure; extracellular fluid; tissue pressure; tissue plasminogen activator; cd31 antigen; paraffin; capillary density; angiogenic proteins |
| Journal Title: | Annals of the Academy of Medicine, Singapore |
| Volume: | 38 |
| Issue: | 12 |
| ISSN: | 0304-4602 |
| Publisher: | Academy Of Medicine Singapore |
| Date Published: | 2009-12-01 |
| Start Page: | 1041 |
| End Page: | 1047 |
| Language: | English |
| PUBMED: | 20052438 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Export Date: 30 November 2010" - "CODEN: AAMSC" - "Source: Scopus" |
Citation Impact
MSK Authors
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13Casas-Ganem -
48
Di Resta -
550Healey -
74
Linkov -
289
Huvos
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