To our knowledge there is, however, no technique available whereby native interstitial fluid can be isolated from solid human tumors. In the search for tumor specific biomarkers the focus should accordingly be on the tumor interstitial environment and the secretome and thus in the fluid phase bathing the tumor cells and the extracellular matrix elements, i.e. Furthermore, proteins secreted from tumor cells and shed membrane proteins will have several orders of magnitude higher concentration in the tumor extracellular or interstitial microenvironment compared to plasma. Many proteins suggested as biomarkers are relatively abundant and related to non-specific global reactions to the disease resulting in low sensitivity and specificity, thus most candidates are never translated into clinical use. However, the high range of protein concentrations in plasma is a major obstacle in biomarker discovery using proteomics. Significant efforts have been invested in the search for biological disease indicators in plasma, for diagnostic and prognostic purposes. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: The authors gratefully acknowledge grants from The Research Council of Norway, The Norwegian Cancer Association and The Western Norway Regional Health Authority. Received: OctoAccepted: MaPublished: April 26, 2011Ĭopyright: © 2011 Haslene-Hox et al. PLoS ONE 6(4):Įditor: Yihai Cao, Karolinska Institutet, Sweden (2011) A New Method for Isolation of Interstitial Fluid from Human Solid Tumors Applied to Proteomic Analysis of Ovarian Carcinoma Tissue. We conclude that the isolated fluid represents undiluted interstitial fluid and thus a subproteome with high concentration of locally secreted proteins that may be detected in plasma for diagnostic, therapeutic and prognostic monitoring by targeted methods.Ĭitation: Haslene-Hox H, Oveland E, Berg KC, Kolmannskog O, Woie K, Salvesen HB, et al. Using a proteomic approach we detected 769 proteins in the isolated interstitial fluid, sixfold higher than in patient plasma. The isolated fluid had a colloid osmotic pressure 79% of that in plasma, suggesting that there was some sieving of proteins at the capillary wall. ![]() The fluid was verified as interstitial by an isolated fluid:plasma ratio not significantly different from 1.0 for both creatinine and Na +, two substances predominantly present in interstitial fluid. Exposure of extirpated tissue to 106 g enabled tumor fluid isolation. ![]() Since tumor interstitial fluid is not readily accessible, we applied a centrifugation method developed in experimental animals and asked whether interstitial fluid from human tissue could be isolated, using ovarian carcinoma as a model. in the tumor interstitial fluid, since the biomarkers are likely to be excreted or derive from the tumor microenvironment. We therefore aimed to develop a technique to search for potential candidate proteins in the proximal proteome, i.e. Focus is shifting towards using proximal fluids for biomarker discovery, but methods to verify the isolated sample's origin are missing. Major efforts have been invested in the identification of cancer biomarkers in plasma, but the extraordinary dynamic range in protein composition, and the dilution of disease specific proteins make discovery in plasma challenging.
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