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Biomechanical study on the process of neovascularization in tumor tissues

肿瘤组织新生血管形成过程的生物力学研究

基本信息

批准号：
08458284
负责人：
OHSHIMA Norio
金额：
$ 4.03万
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：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08458284/
关键词：
peritoneal disseminated tumor model fluorescent tracer Fischer 344 rat peritoneum white blood cell fMLP confocal laser scannity microscopy 蛍光トレーサ法腫瘍微小循環血管新生バイオメカニクス腹膜播種性腫瘍 Hortonの法則

项目摘要

Growth of the tumor tissue is characterized by a marked asgiogenesis in and around the tumor tissues, since tumor cells essentially require supply of nutrients and oxygen and removal of waste metabolites produced by the tumor. Thus, detailed knowledge of the angiogenic process and hemodynamics in the tumor microcirculation is needed to obtain sound guidelines for diagnosis and treatment of malignant tumors. To enable observation of the tumor microvasculature under physiological conditions, we have established a solid-tumor model disseminated into the peritoneal cavity of the rat. We have performed a series of experiments to analyze quantitative features of the vascular architecture of the tumor microvasculature and hemodynamics of the blood flow.To prepare peritoneal disseminated tumor model, 1x107 cells of a colon cancer cell line (RCN-9) were inoculated into peritoneal cavity of male Fischer 344 rats. Four to eleven days after the tumor cell inoculation, the rat was subjected to intravital microscopic observation of the mesenteric microcirculation.The branching pattern of the vascular network was analyzed based on the Horton's law of bifurcation. Accompanied with tumor growth, mesenteric windows showed a marked neovascularization. The neovascularization occurred predominantly in the venular system and the branching pattern of the venular system bacame more complicated.Hemodynamic parameters, i. e.vassel diameter and blood flow velocity, were measured in the mesenteric microvasculature. In microvasculatures of the tumor-bearing rats, the tumor-feeding arterioles and tumor-draining venules were significantly dilated and showed decreased blood flow velocity compared with the microvessels that have no anatomical connection with the tumor.

肿瘤组织的生长的特征在于肿瘤组织中和周围的显著的血管生成，因为肿瘤细胞基本上需要营养物和氧气的供应以及由肿瘤产生的代谢废物的去除。因此，需要详细了解肿瘤微循环中的血管生成过程和血流动力学，以获得诊断和治疗恶性肿瘤的良好指南。为了能够在生理条件下观察肿瘤微血管，我们建立了一种扩散到大鼠腹腔的实体瘤模型。本研究采用1 × 107结肠癌细胞株（RCN-9）接种于雄性Fischer 344大鼠腹腔内，制备腹膜播散性肿瘤模型，并对肿瘤微血管构筑和血流动力学进行定量分析。在接种肿瘤细胞后4 ~ 11天，对大鼠肠系膜微循环进行活体显微镜观察，根据Horton分叉定律分析血管网的分支模式。伴随肿瘤生长，肠系膜窗显示明显的新生血管。新生血管主要发生在微静脉系统，微静脉系统的分支形式较为复杂。在肠系膜微血管中测量血管直径和血流速度。在荷瘤大鼠的微血管中，与与肿瘤没有解剖连接的微血管相比，肿瘤供血动脉和肿瘤引流静脉显著扩张，血流速度降低。