Interstitial Inorganic Phosphate as a Tumor Microenvironment Marker for Tumor Progression

Noninvasive in vivo assessment of chemical tumor microenvironment (TME) parameters such as oxygen ( p O 2 ), extracellular acidosis (pH e ), and concentration of interstitial inorganic phosphate (Pi) may provide unique insights into biological processes in solid tumors. In this work, we employ a rec...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2017-01, Vol.7 (1), p.41233-41233, Article 41233
Main Authors: Bobko, Andrey A., Eubank, Timothy D., Driesschaert, Benoit, Dhimitruka, Ilirian, Evans, Jason, Mohammad, Rahman, Tchekneva, Elena E., Dikov, Mikhail M., Khramtsov, Valery V.
Format: Article
Language:English
Subjects:
631/67/2327
631/67/327
Acidosis
Animal models
Cancer
Correlation analysis
Growth rate
Humanities and Social Sciences
Hypoxia
Metabolism
Metastases
Metastasis
multidisciplinary
Phosphorus
Protons
Science
Solid tumors
Tumorigenesis
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Noninvasive in vivo assessment of chemical tumor microenvironment (TME) parameters such as oxygen ( p O 2 ), extracellular acidosis (pH e ), 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], p O 2 , pH e 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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep41233