title: Expression and functional roles of the chemokine receptor CXCR7 in acute myeloid leukemia cells.
abstract: BACKGROUND
  The C-X-C chemokine receptor 7 (CXCR7) has been shown to be a decoy receptor for CXCR4 in certain cell types. We investigated the expression status and functional roles of CXCR7 in acute myeloid leukemia (AML) cells in vitro.
  
  
  METHODS
  CXCR7 mRNA was knocked down in AML cells by using small interfering RNA (siRNA) technology, and subsequent biological alterations in the cells were evaluated in vitro.
  
  
  RESULTS
  All AML cell lines examined in this study (U937, K562, KG1a, HL-60, and MO7e) and primary CD34(+) cells obtained from patients with AML expressed CXCR7 mRNA at various levels. Western blotting showed that all AML cells produced CXCR7. Furthermore, all AML cells expressed CXCR7 in both the cytoplasm and on the cell surface at various levels. Stromal cell-derived factor-1 (SDF-1; C-X-C motif ligand 12 (CXCL12)) induced internalization of cell surface CXCR7. However, neither hypoxia nor the examined hematopoietic growth factors (interleukin-1β (IL-1β), IL-3, IL-6, granulocyte-colony-stimulating factor, granulocyte, macrophage-colony-stimulating factor, and stem cell factor) and proinflammatory cytokines (interferon-γ, transforming growth factor-β, and tumor necrosis factor-α) were found to alter cell surface CXCR7 expression. The transfection of AML cells with CXCR4 siRNA, but not CXCR7 siRNA, significantly impaired the CXCL12-induced transmigration of the cells. The transfection of AML cells with CXCR7 siRNA did not affect the survival or proliferation of these cells. Knockdown of CXCR7, but not CXCR4, induced the upregulation of CXCL12 mRNA expression and CXCL12 production in AML cells.
  
  
  CONCLUSIONS
  CXCR7 is involved in the regulation of autocrine CXCL12 in AML cells.
authors.affiliation: Department of Drug Activity, New Drug Development Center, Medical Innovation Foundation, Osong, Daejeon, Korea.
authors.forename: Ha-Yon
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: So-Yeon
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Deog-Young
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Moon
authors.affiliation: Department of Internal Medicine, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Yoon-Seok
authors.initials: YS
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Ik-Chan
authors.initials: IC
authors.lastname: Song
authors.affiliation: Department of Internal Medicine, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Hwan-Jung
authors.initials: HJ
authors.lastname: Yun
authors.affiliation: Department of Internal Medicine, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Samyong
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Deog-Yeon
authors.initials: DY
authors.lastname: Jo
keywords: Acute myeloid leukemia; Apoptosis; CXCL12; CXCR7; Cell proliferation; Stromal cell-derived factor-1