title: Interstitial Inorganic Phosphate as a Tumor Microenvironment Marker for Tumor Progression.
abstract: 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, pHeand 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.
authors.affiliation: In Vivo Multifunctional Magnetic Resonance center, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV 26506, United States.|Department of Biochemistry, West Virginia University School of Medicine, Morgantown, WV 26506, United States.
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Bobko
authors.affiliation: In Vivo Multifunctional Magnetic Resonance center, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV 26506, United States.|Department of Microbiology, Immunology &Cell Biology, West Virginia University School of Medicine, Morgantown, WV 26506, United States.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Eubank
authors.affiliation: In Vivo Multifunctional Magnetic Resonance center, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV 26506, United States.|Department of Biochemistry, West Virginia University School of Medicine, Morgantown, WV 26506, United States.
authors.forename: Benoit
authors.initials: B
authors.lastname: Driesschaert
authors.affiliation: Dorothy M. Davis Heart &Lung Research Institute, and Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, United States.
authors.forename: Ilirian
authors.initials: I
authors.lastname: Dhimitruka
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Ohio State University Medical Center, The James Comprehensive Cancer Center, Columbus, OH 43210, United States.
authors.forename: Jason
authors.initials: J
authors.lastname: Evans
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Ohio State University Medical Center, The James Comprehensive Cancer Center, Columbus, OH 43210, United States.
authors.forename: Rahman
authors.initials: R
authors.lastname: Mohammad
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Ohio State University Medical Center, The James Comprehensive Cancer Center, Columbus, OH 43210, United States.
authors.forename: Elena E
authors.initials: EE
authors.lastname: Tchekneva
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Ohio State University Medical Center, The James Comprehensive Cancer Center, Columbus, OH 43210, United States.
authors.forename: Mikhail M
authors.initials: MM
authors.lastname: Dikov
authors.affiliation: In Vivo Multifunctional Magnetic Resonance center, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV 26506, United States.|Department of Biochemistry, West Virginia University School of Medicine, Morgantown, WV 26506, United States.
authors.forename: Valery V
authors.initials: VV
authors.lastname: Khramtsov
mesh_terms: D000138:Acidosis / Q000378:metabolism; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018450:Disease Progression; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D064593:Heterografts; D006801:Humans; D008321:Mammary Glands, Animal / Q000737:chemistry / Q000378:metabolism; D008822:Mice, Transgenic; D010100:Oxygen / Q000032:analysis / Q000378:metabolism; D010710:Phosphates / Q000032:analysis* / Q000378:metabolism; D047368:Tumor Burden; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; D010710:Phosphates; D010100:Oxygen