Effect of Tumor-Specific Leukocyte Behavior on Tumor Growth

利用作者建立的实验性肿瘤模型，对肠系膜微血管的血管生成过程和新生微血管的血流动力学进行了活体显微镜观察。在这个模型中，肿瘤生长伴随着显著的血管生成，显微镜下可以观察到长达10天的时间。移植瘤肠系膜微血管长度明显增加。在新形成的肿瘤血管中，与正常肠系膜小静脉相比，小静脉内白细胞的卷曲和粘连均减弱。为了阐明这些血流动力学行为改变的机制，研究了一氧化氮(NO)在调节肿瘤微循环中的白细胞动力学中的作用。通过抑制一氧化氮合酶(NOS)，肿瘤小静脉中观察到的白细胞-内皮细胞相互作用的基线水平的降低明显增加。这些增加既没有在无肿瘤大鼠身上发现，也没有在荷瘤大鼠的正常微血管中发现。这些结果表明，肿瘤组织中NO的过度产生创造了肿瘤特异性微环境，从而调节了血管生成的肿瘤血管中的白细胞行为。

Using an experimental tumor model developed by the authors, intravital microscopic observations of the angiogenic processes in the mesenteric microvasculature and the hemodynamics of the newly formed microvessels were performed. In this model, tumor growth accompanying a marked angiogenesis was microscopically observable for up to 10 days. The length of the microvessels showed a significant increase in the tumor-bearing mesentery. In the newly formed tumor vessels, rolling and adherence of leukocytes in venules were both attenuated as compared with those in the normal mesenteric venules. To elucidate the mechanisms of these altered behavior of hemodynamics, the role of nitric oxide (NO) in regulating leukocyte dynamics in the tumor microcirculation was examined. Reduction of the baseline levels of leukocyte-endothelial cell interactions observed in the tumor venules were markedly increased by inhibition of NO synthase (NOS). These increases were neither found in the tumor-free rats nor in normal microvessels of the tumor-bearing rats. These results suggest that an excessive production of NO in the tumor tissues creates the tumor-specific microenvironment, thereby modulating leukocyte behavior in the angiogenic tumor vessels.