title: Rgs2 mediates pro-angiogenic function of myeloid derived suppressor cells in the tumor microenvironment via upregulation of MCP-1.
abstract: BACKGROUND
  Tumor growth is intimately linked with stromal interactions. Myeloid derived suppressor cells (MDSCs) are dramatically elevated in cancer patients and tumor bearing mice. MDSCs modulate the tumor microenvironment through attenuating host immune response and increasing vascularization.
  
  
  RESULTS
  In searching for molecular mediators responsible for pro-tumor functions, we found that regulator of G protein signaling-2 (Rgs2) is highly increased in tumor-derived MDSCs compared to control MDSCs. We further demonstrate that hypoxia, a common feature associated with solid tumors, upregulates the gene expression. Genetic deletion of Rgs2 in mice resulted in a significant retardation of tumor growth, and the tumors exhibit decreased vascular density and increased cell death. Interestingly, deletion of Rgs2 in MDSCs completely abolished their tumor promoting function, suggesting that Rgs2 signaling in MDSCs is responsible for the tumor promoting function. Cytokine array profiling identified that Rgs2-/- tumor MDSCs produce less MCP-1, leading to decreased angiogenesis, which could be restored with addition of recombinant MCP-1.
  
  
  CONCLUSIONS
  Our data reveal Rgs2 as a critical regulator of the pro-angiogenic function of MDSCs in the tumor microenvironment, through regulating MCP-1 production.
authors.affiliation: Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Kimberly C
authors.initials: KC
authors.lastname: Boelte
authors.forename: Laura E
authors.initials: LE
authors.lastname: Gordy
authors.forename: Sebastian
authors.initials: S
authors.lastname: Joyce
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Thompson
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: P Charles
authors.initials: PC
authors.lastname: Lin
mesh_terms: D000818:Animals; D016923:Cell Death; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000235:genetics* / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000378:metabolism* / Q000473:pathology*; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D020710:RGS Proteins / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction; D059016:Tumor Microenvironment; D015854:Up-Regulation / Q000235:genetics*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D020710:RGS Proteins; C105345:Rgs2 protein, mouse