VEGF分泌量及分泌来源对肿瘤血管生长影响的数值模拟  

Study on effect of VEGF expression level and sources on tumor-induced angiogenesis by numerical simulation

作　　者：时玉娟[1] 蔡彦[1] 陈强[1] 李志勇[1] 

机构地区：[1]东南大学生物科学与医学工程学院,生物力学实验室,南京210096

出　　处：《医用生物力学》2013年第6期629-635,共7页Journal of Medical Biomechanics

基　　金：国家重点基础研究发展计划973资助项目(2013CB733800);国家自然科学基金资助项目(11272091)

摘　　要：目的数值模拟研究血管内皮生长因子(vascular endothelial growth factor,VEGF)分泌量及分泌来源对肿瘤血管生成的影响。方法建立肿瘤内外血管生成的二维离散数学模型。围绕VEGF的分泌及其诱导新生血管形成肿瘤富血管区的过程,考虑细胞外基质的旁分泌作用以及对内皮细胞运动的趋触作用,以微血管密度作为定量指标,探讨VEGF的分泌量及不同的分泌来源对血管生成的影响。结果肿瘤增殖细胞区、VEGF高浓度区、富血管区三者统一,微血管密度与VEGF的表达有关,随着增殖细胞区域的扩大,即VEGF的表达越来越多,微血管密度也越来越大,但在不同类型的肿瘤中,VEGF不同分泌来源的比重与微血管密度无明显相关性。结论模型探讨了VEGF分泌量及分泌来源对肿瘤血管生成的影响,其中对VEGF的不同分泌来源的考虑可作为研究靶向VEGF治疗肿瘤的模型基础。Objective To investigate the effect of vascular endothelial growth factor （VEGF） expression level and sources on tumor-induced angiogenesis by numerical simulation. Methods A two-dimensional discrete mathematical model of tumor-induced angiogenesis was developed to simulate the growth of microvascular networks inside and outside of the tumor, focusing on endothelial cell proliferation, degradation, random motility, chemotaxis, haptotaxis and stromal-derived VEGF and tumor-derived VEGF. The relationship between VEGF derived by each compartment and tumor microvessel density was discussed. Results The high VEGF region was consistent with proliferating cell and tumor periphery regions in which microvascular density was also high. The simulation demonstrated that an enlargement of proliferating cell region could lead to higher VEGF expression level and higher microvascular density. However, for different types of tumors, the correlations between different VEGF expression sources and microcascular density were not significant. Conclusions The effect of VEGF expression level and source on VEGF-mediated angiogenesis can be investigated by the proposed model. Particularly, taking VEGF expression from different sources into consideration could be a useful modeling tool for anti-VEGF targeted therapies.

关 键 词：肿瘤 血管生成 血管内皮生长因子 分泌量 分泌来源 数值模拟 

分 类 号：R318.01[医药卫生—生物医学工程]