Dexamethasone and hypoxia upregulate CXCR4 expression in myeloma cells

被引：20

作者：

Kim, Seong-Woo ^{[1
]}

Kim, Ha-Yon ^{[1
]}

Lee, Hyo-Jin ^{[1
,2
]}

Yun, Hwan-Jung ^{[1
,2
]}

Kim, Samyong ^{[1
,2
]}

Jo, Deog-Yeon ^{[1
,2
]}

机构：

[1] Chungnam Natl Univ, Coll Med, Dept Internal Med, Div Hematol Oncol, Taejon, South Korea

[2] Daejeon Reg Canc Ctr, Taejon, South Korea

来源：

LEUKEMIA & LYMPHOMA | 2009年 / 50卷 / 07期

关键词：

Multiple myeloma; CXCR4; SDF-1; dexamethasone; hypoxia; ENDOTHELIAL GROWTH-FACTOR; CHEMOKINE RECEPTOR CXCR4; DOWN-REGULATION; HIF-ALPHA; FACTOR-1-ALPHA; MIGRATION; ANGIOGENESIS; ENDOCYTOSIS;

D O I：

10.1080/10428190902893801

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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-beta 1), 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.

引用

页码：1163 / 1173

页数：11

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