Effect of Tumor-Specific Leukocyte Behavior on Tumor Growth

肿瘤特异性白细胞行为对肿瘤生长的影响

• 批准号: 13480287
• 负责人: OHSHIMA Norio
• 金额: $ 8.45万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13480287/
• 关键词: tumor microcirculation; hemodynamics; angiogenesis; nitric oxide; confocal laser-scanning microscope; intravital microscope; leukocyte

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.

使用作者开发的实验性肿瘤模型，对肠系膜微血管中的血管生成过程和新形成的微血管的血流动力学进行了活体显微镜观察。在该模型中，可以在长达 10 天的时间内通过显微镜观察到肿瘤生长伴随着显着的血管生成。荷瘤肠系膜的微血管长度显着增加。在新形成的肿瘤血管中，与正常肠系膜小静脉中的白细胞相比，小静脉中白细胞的滚动和粘附均减弱。为了阐明这些血流动力学行为改变的机制，我们检查了一氧化氮（NO）在调节肿瘤微循环中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-内皮细胞相互作用基线水平的降低显着增加。在无肿瘤大鼠和荷瘤大鼠的正常微血管中均未发现这些增加。这些结果表明，肿瘤组织中NO的过量产生创造了肿瘤特异性微环境，从而调节血管生成肿瘤血管中的白细胞行为。

项目成果

Chika MIYOSHI: "Vascular Endothelial Growth Factor (VEGF) Expression Regulates Angiogenic Growth of Microvasculature in a Peritoneal Disseminated Colon Carcinoma"Biorheology. (in press).

Chika MIYOSHI：“血管内皮生长因子 (VEGF) 表达调节腹膜播散性结肠癌中微血管的血管生成生长”生物流变学。

Lazaro A. LOAIZA: "Electro-acupuncture Stimulation to Muscle Afferents in Anesthetized Rats Modulates the Blood Flow to the Knee Joint through Autonomic Reflexes and Nitric Oxide"Autonomic Neuroscience ; Basic and Clinicals. 97. 103-109 (2002)

Lazaro A. LOAIZA：“电针刺激麻醉大鼠的肌肉传入，通过自主神经反射和一氧化氮调节流向膝关节的血流”自主神经科学；

Chika MTYOSHI: "Tumor-derived Nitric Oxide Attenuates Leukocyte-Endothelial Cell Interactions in the Angiogenic Tumor Vessels"Microcirculation Annual. 18. 107-108 (2002)

Chika MTYOSHI：“肿瘤源性一氧化氮减弱血管生成肿瘤血管中的白细胞-内皮细胞相互作用”微循环年度。

Eri TAGUCHI: "The Relationship between Tumor-derived Nitric Oxide and Tumor Growth"Microcirculation Annual. 18. 109-110 (2002)

田口惠理：《肿瘤源性一氧化氮与肿瘤生长的关系》微循环年鉴。

Chika MIYOSHI: "Vascular Endothelial Growth Factor (VEGF) Expression Regulates Angiogenic Growth of Microvasculature in a Peritoneal Disseminated Colon Carcinoma"Biorheology. 38. 450 (2002)

Chika MIYOSHI：“血管内皮生长因子 (VEGF) 表达调节腹膜播散性结肠癌中微血管的血管生成生长”生物流变学。