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-1beta (IL-1beta),
IL-3,
IL-6,
granulocyte-
colony-stimulating factor, granulocyte,
macrophage-
colony-stimulating factor, and
stem cell factor) and proinflammatory
cytokines (
interferon-gamma,
transforming growth factor-beta, and
tumor necrosis factor-alpha) 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.
CONCLUSION:
CXCR7 is involved in the
regulation of autocrine CXCL12 in AML
cells.