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10.7150/thno.17138

http://scihub22266oqcxt.onion/10.7150/thno.17138
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28744322!5525744!28744322
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suck abstract from ncbi

pmid28744322      Theranostics 2017 ; 7 (9): 2392-2401
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  • Visualization of Tumor-Immune Interaction - Target-Specific Imaging of S100A8/A9 Reveals Pre-Metastatic Niche Establishment #MMPMID28744322
  • Eisenblaetter M; Flores-Borja F; Lee JJ; Wefers C; Smith H; Hueting R; Cooper MS; Blower PJ; Patel D; Rodriguez-Justo M; Milewicz H; Vogl T; Roth J; Tutt A; Schaeffter T; Ng T
  • Theranostics 2017[]; 7 (9): 2392-2401 PMID28744322show ga
  • Background Systemic cancer spread is preceded by the establishment of a permissive microenvironment in the target tissue of metastasis - the premetastatic niche. As crucial players in establishment of the pre-metastatic niche, myeloid derived suppressor cells (MDSC) release S100A8/A9, an exosomal protein that contributes to metastasis, angiogenesis, and immune suppression. We report the application of antibody-based single-photon emission computed tomography (SPECT) for detection of S100A8/A9 in vivo as an imaging marker for pre-metastatic tissue priming. Methods A syngeneic model system for invasive breast cancer with (4T1.2) or without (67NR) the tendency to form lung metastasis was established in BALB/c mice. A SPECT-probe has been generated and tested for visualization of S100A9 release. Tumor-associated changes in numbers and fuction of immune cells in pre-metastatic tissue were evaluated by flow cytometry and confocal microscopy. Results S100A8/A9 imaging reflected MDSC abundance and the establishment of an immunosuppressive environment in pre-metastatic lung tissue (activity 4T1.2 vs. healthy control: 0.95 vs. 0.45 %ID; p<0.001). The S100A8/A9 imaging signal in the pre-metastatic lung correlated with the subsequent metastatic tumor burden in the same organ (r(2)=0.788; p<0.0001). CCL2 blockade and the consecutive inhibition of premetastatic niche establishment was clearly depicted by S100A9-SPECT (lung activity untreated vs. treated: 2 vs, 1.4 %ID). Conclusion We report S100A8/A9 as a potent imaging biomarker for tumor-mediated immune remodeling with potential applications in basic research and clinical oncology.
  • |Animals[MESH]
  • |Breast Neoplasms/*secondary[MESH]
  • |Calgranulin A/*analysis[MESH]
  • |Calgranulin B/*analysis[MESH]
  • |Disease Models, Animal[MESH]
  • |Flow Cytometry[MESH]
  • |Lung Neoplasms/*secondary[MESH]
  • |Mice, Inbred BALB C[MESH]
  • |Microscopy, Confocal[MESH]
  • |Neoplasm Metastasis/*diagnostic imaging[MESH]


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