Angiogenesis, microvascular architecture, microhemodynamics, and interstitial fluid pressure during early growth of human adenocarcinoma LS174T in SCID mice.
Angiogenesis, microvascular architecture, microhemodynamics, and interstitial fluid pressure during early growth of human adenocarcinoma LS174T in SCID mice.
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发表时间：
1992-12
期刊：
影响因子：
11.2
通讯作者：
M. Leunig;F. Yuan;M. Menger;Y. Boucher;A. Goetz;K. Messmer;R. Jain
中科院分区：
文献类型：
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作者：
M. Leunig;F. Yuan;M. Menger;Y. Boucher;A. Goetz;K. Messmer;R. Jain
迄今为止，大多数关于肿瘤血管生成、微循环和转运的定量信息来自于在透明室制备物中生长的啮齿动物肿瘤。在本文中，我们提出了一种适用于免疫缺陷小鼠的人肿瘤异种移植物研究的小室技术。采用活体显微镜和图像分析技术对背部皮肤褶皱室制备的严重联合免疫缺陷小鼠的微循环参数进行定量。人结肠腺癌LS 174 T在小室制备中的捕获率为100%，肿瘤面积倍增时间为6.5天。将2 × 105个肿瘤细胞植入皮肤横纹肌后3天，在肿瘤细胞团中观察到毛细血管芽。10天后，肿瘤中的微血管建立。在第10、14、18和22天测量的毛细血管密度、血管直径、红细胞速度和单个微血管中的血流速率在横纹肌中没有统计学差异（毛细血管）和皮下组织无肿瘤动物（N = 6）的皮肤（小动脉和小静脉）的参数增加，而这些参数略有增加，但不显著，在LS 174 T肿瘤中（N = 7）。这些小肿瘤的平均间质液压力（+/- SD）在第10天为4.6 +/- 1.7 mmHg（N = 4），在第22天为5.1 +/- 0.9 mmHg（N = 4），与皮下和皮肤组织（-0.9 +/- 0.8 mmHg）相比显著升高（N = 4）（P < 0.001）。据我们所知，这是第一个模型，使人肿瘤异种移植物在一个透明的腔室制备在严重的联合免疫缺陷小鼠的活体显微镜研究。研究血管生成，微循环和运输使用这样的准备应提供新的见解微循环介导的机制，癌症治疗。
To date, most quantitative information on tumor angiogenesis, microcirculation, and transport has been derived from rodent tumors grown in transparent chamber preparations. In this paper we present a chamber technique adapted to immunodeficient mice for the study of human tumor xenografts. Microcirculatory parameters in severe combined immunodeficient mice bearing a dorsal skin fold chamber preparation were quantified using intravital microscopy and image analysis. The take rate of the human colon adenocarcinoma LS174T in the chamber preparation was 100%, and the tumor area doubling time was 6.5 days. Three days following implantation of 2 x 10(5) tumor cells onto the striated skin muscle, capillary sprouts were noted in the tumor cell mass. Microvasculature in the tumors was established after 10 days. Capillary density, vessel diameter, red blood cell velocity, and blood flow rates in individual microvessels measured on days 10, 14, 18, and 22 showed no statistical difference in the striated muscle (capillaries) and subcutaneous tissue (arterioles and venules) of the skin of tumor-free animals (N = 6), whereas these parameters increased slightly, but not significantly, in the LS174T tumors (N = 7). Mean interstitial fluid pressure (+/- SD) in these small tumors was 4.6 +/- 1.7 mmHg (N = 4) on day 10 and 5.1 +/- 0.9 mmHg (N = 4) on day 22 and significantly elevated compared to that in the subcutaneous and skin tissue (-0.9 +/- 0.8 mmHg) (N = 4) (P < 0.001). To our knowledge, this is the first model enabling intravital microscopic studies of human tumor xenografts in a transparent chamber preparation in severe combined immunodeficient mice. Studies on angiogenesis, microcirculation, and transport using such a preparation should provide new insights into microcirculation-mediated mechanisms for cancer treatment.