Dexamethasone and hypoxia upregulate CXCR4 expression in myeloma cells.
We investigated the modulation of CXCR4 expression by cytokines, dexamethasone, and hypoxia in myeloma cells in vitro. Tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1), and vascular endothelial growth factor (VEGF) enhanced CXCR4 expression in RPMI8226 cells. In the myeloma cell lines examined and primary bone marrow (BM) CD138+ cells, dexamethasone enhanced CXCR4 expression both in the cytoplasm and on the cell surface, while downregulating SDF-1 expression and secretion in BM stromal cells. Incubation of cells under hypoxic conditions (1% O(2)) also induced upregulation of CXCR4 in the cytoplasm and on the cell surface and enhanced chemotaxis in response to stromal cell-derived factor-1 (SDF-1). Cell surface CXCR4 expression was more prominent in annexin V-positive apoptotic cells. Given the roles of the SDF-1/CXCR4 axis in the development and progression of myeloma, CXCR4-downregulating agents may enhance the antitumor effects of dexamethasone.
Kim
Seong-Woo
SW
Division of Hematology/Oncology, Department of Internal Medicine, College of Medicine, Chungnam National University, Jung-gu, Daejeon, Korea.
Kim
Ha-Yon
HY
Lee
Hyo-Jin
HJ
Yun
Hwan-Jung
HJ
Kim
Samyong
S
Jo
Deog-Yeon
DY
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D002462:Cell Membrane / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005434:Flow Cytometry / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia; D015850:Interleukin-6 / Q000378:metabolism; D008856:Microscopy, Fluorescence / Q000379:methods; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism / Q000502:physiology*; D053668:Syndecan-1 / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018931:Antineoplastic Agents, Hormonal; D015850:Interleukin-6; D019718:Receptors, CXCR4; D053668:Syndecan-1; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone