Yuan F, Salehi H A, Boucher Y, Vasthare U S, Tuma R F, Jain R K
Department of Radiation Oncology, Massachusetts General Hospital, Boston 02114.
Cancer Res. 1994 Sep 1;54(17):4564-8.
Many brain tumors are highly resistant to chemotherapy, presumably due to the presence of a tight blood-tumor barrier. For a better understanding of the regulation of this barrier by the brain environment, a new intravital microscopy model was established by transplanting tumor tissue into cranial windows in both rats and mice. The model was characterized by RBC velocities, vessel diameters, and vascular permeabilities of various tumors: R3230AC (a rat mammary adenocarcinoma), MCaIV (a mouse mammary adenocarcinoma), and U87 and HGL21 (human malignant astrocytomas). Our results showed that tumor blood flow in cranial windows was one to three orders of magnitude lower than the blood flow in pial vessels and similar to that in dorsal skin-fold chambers observed in previous studies. The mean vessel diameter ranged from 6.8 +/- 1.3 microns for HGL21 to 30.4 +/- 8.5 microns for MCaIV. At least one order of magnitude difference in vascular permeability to albumin was observed between tumor lines: 0.11 +/- 0.05 x 10(-7) cm/s for HGL21 versus 3.8 +/- 1.2 x 10(-7) cm/s for U87. The low vascular permeability of HGL21, which was also confirmed by both sodium fluorescein and Lissamine green injections, suggests that not all tumors are leaky to tracer molecules and that the blood-tumor barrier of this tumor still possesses some characteristics of blood-brain barrier as observed in other intracranial tumors. The model presented here will allow us to manipulate the vascular permeability in brain tumors and thus may provide new information on the regulation of the blood-tumor barrier and new strategies for improving drug delivery in brain tumors.
许多脑肿瘤对化疗具有高度抗性，可能是由于存在紧密的血瘤屏障。为了更好地理解脑环境对该屏障的调节作用，通过将肿瘤组织移植到大鼠和小鼠的颅骨窗口中，建立了一种新的活体显微镜模型。该模型的特征在于各种肿瘤的红细胞速度、血管直径和血管通透性：R3230AC（大鼠乳腺腺癌）、MCaIV（小鼠乳腺腺癌）以及U87和HGL21（人类恶性星形细胞瘤）。我们的结果表明，颅骨窗口中的肿瘤血流比软脑膜血管中的血流低一到三个数量级，与先前研究中在背部皮肤褶皱腔中观察到的血流相似。平均血管直径范围从HGL21的6.8±1.3微米到MCaIV的30.4±8.5微米。在不同肿瘤系之间观察到血管对白蛋白的通透性至少有一个数量级的差异：HGL21为0.11±0.05×10⁻⁷厘米/秒，而U87为3.8±1.2×10⁻⁷厘米/秒。HGL21的低血管通透性通过荧光素钠和丽丝胺绿注射也得到了证实，这表明并非所有肿瘤对示踪分子都是渗漏的，并且该肿瘤的血瘤屏障仍然具有其他颅内肿瘤中观察到的血脑屏障的一些特征。这里介绍的模型将使我们能够操纵脑肿瘤中的血管通透性，从而可能提供关于血瘤屏障调节的新信息以及改善脑肿瘤药物递送策略的新信息。
