Interstitial Inorganic Phosphate as a Tumor Microenvironment Marker for Tumor Progression.
Interstitial Inorganic Phosphate as a Tumor Microenvironment Marker for Tumor Progression.
复制标题
间质性无机磷酸盐作为肿瘤进展的肿瘤微环境标记。
DOI：
10.1038/srep41233
复制
发表时间：
2017-01-24
影响因子：
4.6
通讯作者：
Khramtsov VV
中科院分区：
文献类型：
--
作者：
Bobko AA;Eubank TD;Driesschaert B;Dhimitruka I;Evans J;Mohammad R;Tchekneva EE;Dikov MM;Khramtsov VV
化学肿瘤微环境（TME）参数，如氧（pO2），细胞外酸中毒（pHe），和间质无机磷酸盐（Pi）的浓度的非侵入性体内评估可以提供独特的见解，在实体瘤的生物过程。在这项工作中，我们采用了最近开发的多功能三苯甲基顺磁探针和电子顺磁共振（EPR）技术在体内并行评估这些TME参数在各种小鼠模型的癌症。虽然数据支持TME中存在缺氧和酸性区域，但对于间质Pi观察到最显著的差异，肿瘤中的浓度比正常组织高约2倍，间质Pi是唯一允许区分非转移性和高转移性肿瘤的参数。[Pi]、pO2、pHe与肿瘤体积之间的相关性分析揭示了高[Pi]与肿瘤代谢变化的关联，并支持质子和Pi在TME中积聚的不同机制。我们的数据将间质无机磷酸盐确定为肿瘤进展的新TME标志物。Pi与肿瘤代谢、缓冲液介导的质子转运以及“生长速率假说”中快速生长所需的高磷含量的关联可能强调其在肿瘤发生和肿瘤进展中的潜在作用。
Noninvasive in vivo assessment of chemical tumor microenvironment (TME) parameters such as oxygen (pO2), extracellular acidosis (pHe), and concentration of interstitial inorganic phosphate (Pi) may provide unique insights into biological processes in solid tumors. In this work, we employ a recently developed multifunctional trityl paramagnetic probe and electron paramagnetic resonance (EPR) technique for in vivo concurrent assessment of these TME parameters in various mouse models of cancer. While the data support the existence of hypoxic and acidic regions in TME, the most dramatic differences, about 2-fold higher concentrations in tumors vs. normal tissues, were observed for interstitial Pi - the only parameter that also allowed for discrimination between non-metastatic and highly metastatic tumors. Correlation analysis between [Pi], pO2, pHe and tumor volumes reveal an association of high [Pi] with changes in tumor metabolism and supports different mechanisms of protons and Pi accumulation in TME. Our data identifies interstitial inorganic phosphate as a new TME marker for tumor progression. Pi association with tumor metabolism, buffer-mediated proton transport, and a requirement of high phosphorus content for the rapid growth in the “growth rate hypothesis” may underline its potential role in tumorigenesis and tumor progression.