Functional imaging of the angiogenic switch in a transgenic mouse model of human breast cancer by dynamic contrast enhanced magnetic resonance imaging
Functional imaging of the angiogenic switch in a transgenic mouse model of human breast cancer by dynamic contrast enhanced magnetic resonance imaging
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DOI：
10.1002/ijc.30073
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发表时间：
2016-07-15
影响因子：
6.4
通讯作者：
Aime, Silvio
中科院分区：
文献类型：
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作者：
Consolino, Lorena;Longo, Dario Livio;Aime, Silvio
肿瘤的进展依赖于几个连续的事件，包括微环境重塑过程和向血管生成表型的转换，导致新血管的招募。非侵入性成像技术可以监测肿瘤血管和细胞性的功能变化。这项工作的目的是通过动态对比增强(DCE)和扩散加权(DW)磁共振成像(MRI)方法检测转基因小鼠模型(BALB-Neut小鼠)乳腺癌发生和发展过程中血管形成和细胞数量的功能变化。组织学检查显示，BALB-Neut乳腺经历了从单纯增生到浸润性癌的缓慢癌变过程，但仍保留了乳腺的正常部分。DCE-MRI结果显示，与BALB/c相比，BALB-Neut增生性乳腺在血管通透性(K-tran，容量转移常数)和血管化(v(P)，血管体积分数)方面发生了显著的功能变化。当乳腺组织从单纯增生发展到不典型增生时，BALB-Neut小鼠的DCE-MRI生物标志物比BALB/c小鼠显著增加(BALB-Neut和BALB/c小鼠的K-ans分别为5.3+/-0.7E-4和3.1+/-0.5E-4；v(P)=7.4+/-0.8E-2和4.7+/-0.6E-2)，在肿瘤转化的连续步骤中保持不变。与DCE-MRI观察一致，微血管计数显示肿瘤血管显著增加。我们的研究表明，DCE-MRI估计可以准确地检测乳腺癌发生的早期阶段的血管生成开关。这些结果支持这样一种观点，即这种成像方法是表征微血管变化的一个很好的工具，尽管在转基因小鼠模型中只有一小部分乳腺发生了肿瘤病变。
Tumour progression depends on several sequential events that include the microenvironment remodelling processes and the switch to the angiogenic phenotype, leading to new blood vessels recruitment. Non-invasive imaging techniques allow the monitoring of functional alterations in tumour vascularity and cellularity. The aim of this work was to detect functional changes in vascularisation and cellularity through Dynamic Contrast Enhanced (DCE) and Diffusion Weighted (DW) Magnetic Resonance Imaging (MRI) modalities during breast cancer initiation and progression of a transgenic mouse model (BALB-neuT mice). Histological examination showed that BALB-neuT mammary glands undergo a slow neoplastic progression from simple hyperplasia to invasive carcinoma, still preserving normal parts of mammary glands. DCE-MRI results highlighted marked functional changes in terms of vessel permeability (K-trans, volume transfer constant) and vascularisation (v(p), vascular volume fraction) in BALB-neuT hyperplastic mammary glands if compared to BALB/c ones. When breast tissue progressed from simple to atypical hyperplasia, a strong increase in DCE-MRI biomarkers was observed in BALB-neuT in comparison to BALB/c mice (K-trans = 5.3 +/- 0.7E-4 and 3.1 +/- 0.5E-4; v(p) = 7.4 +/- 0.8E-2 and 4.7 +/- 0.6E-2 for BALB-neuT and BALB/c, respectively) that remained constant during the successive steps of the neoplastic transformation. Consistent with DCE-MRI observations, micro vessel counting revealed a significant increase in tumour vessels. Our study showed that DCE-MRI estimates can accurately detect the angiogenic switch at early step of breast cancer carcinogenesis. These results support the view that this imaging approach is an excellent tool to characterize microvasculature changes, despite only small portions of the mammary glands developed neoplastic lesions in a transgenic mouse model.