Stohrer M, Boucher Y, Stangassinger M, Jain R K
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Cancer Res. 2000 Aug 1;60(15):4251-5.
Oncotic and hydrostatic pressure differences control the movement of fluid and large molecules across the microvascular wall of normal and tumor tissues. Recent studies have shown that the interstitial fluid pressure in tumors is elevated and is approximately equal to the microvascular pressure. Whereas oncotic pressure in blood plasma of various species is known, no data are available on the oncotic pressure in the interstitial space of tumors. We hypothesize that because of the leaky nature of tumor vessels, oncotic pressure in tumor interstitium should be close to that in plasma. To this end, we first developed a chronic wick method for the direct measurement of oncotic pressures in the interstitial fluid of tumors grown in mice. We found interstitial oncotic pressures in four human tumor xenografts to be higher than in s.c. tissue and comparable to that in plasma [rhabdomyosarcoma (RD), 24.2+/-4.7; squamous cell carcinoma (FaDu), 19.9+/-1.9; small cell lung carcinoma (54A), 21.1+/-2.8; colon adenocarcinoma (LIS174T), 16.7+/-3.0 mm Hg; s.c. tissue, 8.2+/-2.3; plasma, 20.0+/-1.6 mm Hg]. These results support our hypothesis that the oncotic pressure difference across the tumor microvascular wall is low. The high oncotic pressure in tumors is consistent with the elevated interstitial fluid pressure, and it contributes to the suboptimal delivery of large therapeutic agents to neoplastic cells.
胶体渗透压和流体静压的差异控制着液体和大分子在正常组织及肿瘤组织微血管壁间的移动。最近的研究表明，肿瘤组织中的间质液压力升高，且大约等于微血管压力。虽然已知不同物种血浆中的胶体渗透压，但尚无关于肿瘤间质空间中胶体渗透压的数据。我们推测，由于肿瘤血管的渗漏特性，肿瘤间质中的胶体渗透压应与血浆中的相近。为此，我们首先开发了一种慢性灯芯法，用于直接测量小鼠体内生长肿瘤的间质液中的胶体渗透压。我们发现，四种人肿瘤异种移植瘤的间质胶体渗透压高于皮下组织，且与血浆中的相近[横纹肌肉瘤（RD），24.2±4.7；鳞状细胞癌（FaDu），19.9±1.9；小细胞肺癌（54A），21.1±2.8；结肠腺癌（LIS174T），16.7±3.0 mmHg；皮下组织，8.2±2.3；血浆，20.0±1.6 mmHg]。这些结果支持了我们的假设，即肿瘤微血管壁上的胶体渗透压差异较低。肿瘤中较高的胶体渗透压与升高的间质液压力一致，并且它导致大型治疗药物向肿瘤细胞的递送效果欠佳。
