Mary Ann Arildsen
Faculty Member
Last active: 6/27/2014

Rgs2 mediates pro-angiogenic function of myeloid derived suppressor cells in the tumor microenvironment via upregulation of MCP-1.

Boelte KC, Gordy LE, Joyce S, Thompson MA, Yang L, Lin PC
PLoS One. 2011 6 (4): e18534

PMID: 21494556 · PMCID: PMC3073977 · DOI:10.1371/journal.pone.0018534

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.

METHODOLOGY/PRINCIPAL FINDINGS - 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.

CONCLUSION - Our data reveal Rgs2 as a critical regulator of the pro-angiogenic function of MDSCs in the tumor microenvironment, through regulating MCP-1 production.

MeSH Terms (19)

Animals Cell Death Cell Differentiation Cell Movement Cell Proliferation Chemokine CCL2 Endothelial Cells Gene Deletion Gene Expression Regulation, Neoplastic Humans Mice Mice, Inbred C57BL Myeloid Cells Neoplasms Neovascularization, Pathologic RGS Proteins Signal Transduction Tumor Microenvironment Up-Regulation

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