PMID- 19391039 OWN - NLM STAT- MEDLINE DCOM- 20090902 LR - 20190116 IS - 1029-2403 (Electronic) IS - 1026-8022 (Linking) VI - 50 IP - 7 DP - 2009 Jul TI - Dexamethasone and hypoxia upregulate CXCR4 expression in myeloma cells. PG - 1163-73 LID - 10.1080/10428190902893801 [doi] AB - 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. FAU - Kim, Seong-Woo AU - Kim SW AD - Division of Hematology/Oncology, Department of Internal Medicine, College of Medicine, Chungnam National University, Jung-gu, Daejeon, Korea. FAU - Kim, Ha-Yon AU - Kim HY FAU - Lee, Hyo-Jin AU - Lee HJ FAU - Yun, Hwan-Jung AU - Yun HJ FAU - Kim, Samyong AU - Kim S FAU - Jo, Deog-Yeon AU - Jo DY LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 RN - 0 (Antineoplastic Agents, Hormonal) RN - 0 (Interleukin-6) RN - 0 (Receptors, CXCR4) RN - 0 (Syndecan-1) RN - 0 (Transforming Growth Factor beta1) RN - 0 (Tumor Necrosis Factor-alpha) RN - 7S5I7G3JQL (Dexamethasone) SB - IM CIN - Leuk Lymphoma. 2009 Jul;50(7):1067-8. PMID: 19557626 MH - Antineoplastic Agents, Hormonal/*pharmacology MH - Bone Marrow Cells/cytology MH - Cell Membrane/metabolism MH - Dexamethasone/*pharmacology MH - Flow Cytometry/methods MH - Gene Expression Regulation, Neoplastic MH - Humans MH - *Hypoxia MH - Interleukin-6/metabolism MH - Microscopy, Fluorescence/methods MH - Multiple Myeloma/*drug therapy/*metabolism MH - Receptors, CXCR4/metabolism/*physiology MH - Syndecan-1/biosynthesis MH - Transforming Growth Factor beta1/metabolism MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2009/04/25 09:00 MHDA- 2009/09/03 06:00 CRDT- 2009/04/25 09:00 PHST- 2009/04/25 09:00 [entrez] PHST- 2009/04/25 09:00 [pubmed] PHST- 2009/09/03 06:00 [medline] AID - 910664047 [pii] AID - 10.1080/10428190902893801 [doi] PST - ppublish SO - Leuk Lymphoma. 2009 Jul;50(7):1163-73. doi: 10.1080/10428190902893801.