Tumor vascular permeability to a nanoprobe correlates to tumor-specific expression levels of angiogenic markers.
Tumor vascular permeability to a nanoprobe correlates to tumor-specific expression levels of angiogenic markers.
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DOI：
10.1371/journal.pone.0005843
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发表时间：
2009-06-09
期刊：
影响因子：
3.7
通讯作者：
Bellamkonda RV
中科院分区：
文献类型：
--
作者：
Karathanasis E;Chan L;Karumbaiah L;McNeeley K;D'Orsi CJ;Annapragada AV;Sechopoulos I;Bellamkonda RV
血管内皮生长因子（VEGF）受体-2是VEGF对乳腺肿瘤的促有丝分裂、血管生成和血管通透性增高作用的主要介质。VEGF和VEGF受体2的过度表达与肿瘤组织的病理形态学程度和预后不良有关。在这项研究中，我们证明了肿瘤血管对纳米探针的渗透性程度的非侵入性定量与VEGF及其受体水平和肿瘤生长相关。我们设计了一种成像纳米探针和一种使用乳房X线摄影术检测100 nm尺度纳米探针的肿瘤内沉积的方法，允许测量大鼠MAT B III乳腺肿瘤模型中的肿瘤血管通透性。肿瘤血管通透性在动物间差异很大。值得注意的是，如通过qRT-PCR测量的肿瘤的VEGF和VEGF受体-2基因表达显示出与基于成像的对100 nm尺度纳米探针的血管渗透性的测量的强相关性。这与具有高血管生成活性的肿瘤预期具有更可渗透的血管导致纳米级试剂的高肿瘤内沉积的事实非常一致。此外，我们发现，用乳房X线摄影成像的纳米探针的更高的肿瘤内沉积与更快的肿瘤生长速率相关。该数据表明血管通透性与肿瘤生长成比例，并且肿瘤血管通透性可以是个体肿瘤中潜在的VEGF和VEGF受体-2表达的量度。据我们所知，这是第一次证明，肿瘤血管对纳米探针的渗透性的定量成像代表了血管生成的潜在分子标志物的替代、功能性生物标志物的一种形式。
Vascular endothelial growth factor (VEGF) receptor-2 is the major mediator of the mitogenic, angiogenic, and vascular hyperpermeability effects of VEGF on breast tumors. Overexpression of VEGF and VEGF receptor-2 is associated with the degree of pathomorphosis of the tumor tissue and unfavorable prognosis. In this study, we demonstrate that non-invasive quantification of the degree of tumor vascular permeability to a nanoprobe correlates with the VEGF and its receptor levels and tumor growth. We designed an imaging nanoprobe and a methodology to detect the intratumoral deposition of a 100 nm-scale nanoprobe using mammography allowing measurement of the tumor vascular permeability in a rat MAT B III breast tumor model. The tumor vascular permeability varied widely among the animals. Notably, the VEGF and VEGF receptor-2 gene expression of the tumors as measured by qRT-PCR displayed a strong correlation to the imaging-based measurements of vascular permeability to the 100 nm-scale nanoprobe. This is in good agreement with the fact that tumors with high angiogenic activity are expected to have more permeable blood vessels resulting in high intratumoral deposition of a nanoscale agent. In addition, we show that higher intratumoral deposition of the nanoprobe as imaged with mammography correlated to a faster tumor growth rate. This data suggest that vascular permeability scales to the tumor growth and that tumor vascular permeability can be a measure of underlying VEGF and VEGF receptor-2 expression in individual tumors. This is the first demonstration, to our knowledge, that quantitative imaging of tumor vascular permeability to a nanoprobe represents a form of a surrogate, functional biomarker of underlying molecular markers of angiogenesis.
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影响因子：
5
作者：
Heffelfinger, SC;Yan, M;Warshawsky, D
通讯作者：
Warshawsky, D
影响因子：
3.1
作者：
Chen, Kai;Cai, Weibo;Chen, Xiaoyuan
通讯作者：
Chen, Xiaoyuan
影响因子：
14
作者：
Karathanasis, Efstathios;Chan, Leslie;Bellamkonda, Ravi V.
通讯作者：
Bellamkonda, Ravi V.
影响因子：
3.3
作者：
LARSSON, HBW;STUBGAARD, M;PAULSON, OB
通讯作者：
PAULSON, OB
DOI：
10.1093/jnci/72.1.31
发表时间：
1984-01-01
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
BROWN, BW;ATKINSON, EN;MONTAGUE, ED
通讯作者：
MONTAGUE, ED