Musculoskeletal Oncology Service, Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Ann Acad Med Singap. 2009 Dec;38(12):1041-7.
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.
Sixteen patients with the clinical diagnosis of osteosarcomas underwent blood fl ow 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 pressurised cell culture system.
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.
Our data suggest that some molecules in angiogenesis are regulated by changes in IFP.
我们之前已经表明，骨肉瘤存在间质液压（IFP）升高的状态，这与增殖和化疗敏感性增加有关。在这项研究中，我们假设骨肉瘤中持续升高的 IFP 会调节血管生成。
16 名临床诊断为骨肉瘤的患者在开放式活检时和位置处通过针内wick 法进行血流和 IFP 读数。血管生成通过活检标本中的毛细血管密度确定。我们对活检样本的石蜡包埋组织块进行 CD31、VEGF-A、VEGF-C 和 TPA 的免疫组织化学染色的数字图像分析。临床结果在加压细胞培养系统中得到验证。
肿瘤中的 IFP（平均值 33.5 +/- SD 17.2 mmHg）明显高于正常组织（2.9 +/- 5.7 mmHg）（P = 0.00001）。低血管生成肿瘤的压力读数明显高于高血管生成肿瘤（P <0.001）。在骨肉瘤细胞系中，在加压环境中的生长与 VEGF-A 下调、VEGF-C 上调和 TPA 上调相关。在 OB 细胞系中则相反。在加压环境中，HUVEC 细胞系的生长并没有明显受到抑制。免疫组织化学评估 VEGF-A（P = 0.01）、VEGF-C（P = 0.008）和 TPA（P = 0.0001）的翻译与 PCR 的发现一致。
我们的数据表明，血管生成中的一些分子受 IFP 变化的调节。
