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November 30, 2015

Interactome analysis of myeloid-derived suppressor cells in murine models of colon and breast cancer. Oncotarget.

Written and published by Biogerontology Research Foundation staff in collaboration with HiBiotechnology LLC and Federal Clinical Research Center of Pediatric Hematology, Oncology and Immunology.

Interactome analysis of myeloid-derived suppressor cells in murine models of colon and breast cancer. Oncotarget. 2014 Nov 30;5(22):11345-53.

Aliper AM(1), Frieden-Korovkina VP(2), Buzdin A(3), Roumiantsev SA(4), Zhavoronkov A(5).

(1) Federal Clinical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia. Insilico Medicine, Inc., Johns Hopkins University, Baltimore, MD, USA.

(2) HiBiotechnology, LLC, Wellman, Iowa City, Iowa, USA.

(3) Federal Clinical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya, Moscow, Russia. Pathway Pharmaceuticals, Limited, Wan Chai, Hong Kong.

(4) Federal Clinical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia. Pirogov Russian National Research Medical University, Moscow, Russia. Moscow Institute of Physics and Technology, Dolgoprudny, Moscow, Russian.

(5) Federal Clinical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia. Insilico Medicine, Inc., Johns Hopkins University, Baltimore, MD, USA. Moscow Institute of Physics and Technology, Dolgoprudny, Moscow, Russian. The Biogerontology Research Foundation, BGRF, London, UK.

Abstract: In solid cancers, myeloid derived suppressor cells (MDSC) infiltrate (peri)tumoral tissues to induce immune tolerance and hence to establish a microenvironment permissive to tumor growth. Importantly, the mechanisms that facilitate such infiltration or a subsequent immune suppression are not fully understood. Hence, in this study, we aimed to delineate disparate molecular pathways which MDSC utilize in murine models of colon or breast cancer. Using pathways enrichment analysis, we completed interactome maps of multiple signaling pathways in CD11b+/Gr1(high/low) MDSC from spleens and tumor infiltrates of mice with c26GM colon cancer and tumor infiltrates of MDSC in 4T1 breast cancer. In both cancer models, infiltrating MDSC, but not CD11b+ splenic cells, have been found to be enriched in multiple signaling molecules suggestive of their enhanced proliferative and invasive phenotypes. The interactome data has been subsequently used to reconstruct a previously unexplored regulation of MDSC cell cycle by the c-myc transcription factor which was predicted by the analysis. Thus, this study represents a first interactome mapping of distinct multiple molecular pathways whereby MDSC sustain cancer progression.

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