Data from: D quantification of tumor vasculature in lymphoma xenografts in NOD/SCID mice allows to detect differences among vascular-targeted therapies

Quantitative characterization of the in vivo effects of vascular-targeted therapies on tumor vessels is hampered by the absence of useful 3D vascular network descriptors aside from microvessel density. In this study, we extended the quantification of planar vessel distribution to the analysis of vascular volumes by studying the effects of antiangiogenic (sorafenib and sunitinib) or antivascular (combretastatin A4 phosphate) treatments on the quantity and spatial distributions of thin microvessels. These observations were restricted to perinecrotic areas of treated human multiple myeloma tumors xenografted in immunodeficient mice and to microvessels with an approximate cross-sectional area lower than 75 µm2. Finally, vessel skeletonization minimized artifacts due to possible differential wall staining and allowed a comparison of the various treatment effects. Antiangiogenic drug treatment reduced the number of vessels of every caliber (at least 2-fold fewer vessels vs. controls; p<0.001, n = 8) and caused a heterogeneous distribution of the remaining vessels. In contrast, the effects of combretastatin A4 phosphate mainly appeared to be restricted to a homogeneous reduction in the number of thin microvessels (not more than 2-fold less vs. controls; p<0.001, n = 8) with marginal effects on spatial distribution. Unexpectedly, these results also highlighted a strict relationship between microvessel quantity, distribution and cross-sectional area. Treatment-specific changes in the curves describing this relationship were consistent with the effects ascribed to the different drugs. This finding suggests that our results can highlight differences among vascular-targeted therapies, providing hints on the processes underlying sample vascularization together with the detailed characterization of a pathological vascular tree.

目前除微血管密度（microvessel density）外，尚无有效的三维血管网络表征指标，这极大限制了血管靶向疗法对肿瘤血管在体效应的定量表征研究。本研究将平面血管分布量化分析拓展至血管体积分析，针对抗血管生成（antiangiogenic）疗法（索拉非尼（sorafenib）、舒尼替尼（sunitinib））与抗血管（antivascular）疗法（康普瑞汀A4磷酸酯（combretastatin A4 phosphate））对细小微血管的数量及空间分布的影响开展研究。本研究观测范围限定于免疫缺陷小鼠体内异种移植的经药物处理的人多发性骨髓瘤（multiple myeloma）肿瘤的坏死周边区域，以及横截面积约小于75 µm²的微血管。最终，血管骨架化（vessel skeletonization）处理可最大程度消除因血管壁染色差异可能产生的伪影，从而实现不同药物处理效应的对比分析。抗血管生成药物处理可降低所有口径血管的数量（较对照组至少减少2倍；p<0.001，n=8），并使剩余血管呈现异质性分布。与之相反，康普瑞汀A4磷酸酯的效应主要局限于细小微血管数量的均一性减少（较对照组减少不超过2倍；p<0.001，n=8），对空间分布的影响较为微弱。出乎意料的是，本研究结果还揭示了微血管数量、分布与横截面积之间存在严格的关联。描述该关联的曲线在不同药物处理组间出现的特异性变化，与不同药物的已知效应相符。该发现表明，本研究结果可有效区分不同血管靶向疗法的差异，为揭示样本血管生成的潜在机制提供线索，同时实现病理性血管树（pathological vascular tree）的精细化表征。