Granulocyte colony-stimulating factor enhances bone tumor growth in mice in an osteoclast-dependent manner
Granulocyte colony-stimulating factor enhances bone tumor growth in mice in an osteoclast-dependent manner
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DOI：
10.1182/blood-2006-09-048686
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发表时间：
2007-04-15
期刊：
影响因子：
20.3
通讯作者：
Weilbaecher, Katherine
中科院分区：
文献类型：
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作者：
Hirbe, Angela C.;Uluckan, Ozge;Weilbaecher, Katherine
在动物模型中，破骨细胞（OC）活性的抑制与骨中肿瘤生长的减少有关。对促进癌症患者骨吸收的因素认识的增加使我们研究OC活化的增加是否能促进骨中肿瘤的生长。粒细胞集落刺激因子（G-CSF）用于治疗化疗诱导的中性粒细胞减少症，但也与OC活性标志物增加和骨矿物质密度（BMD）降低相关。我们使用G-CSIF作为一种工具来研究OC活性增加对2种小鼠溶骨性肿瘤模型中肿瘤生长的影响。单独使用G-CSF（不进行化疗）8天可显著降低小鼠骨密度，并增加骨沿着骨的OC周长。通过体内生物发光成像和组织学骨髓肿瘤分析定量，单独给予G-CSF的小鼠显示骨中肿瘤生长显著增加。短期给予AMD 3100（一种CXCR 4抑制剂，可动员中性粒细胞，对骨吸收影响不大）不会导致肿瘤负荷增加。然而，OC缺陷型骨保护素转基因（OPG（Tg））小鼠和双膦酸盐治疗小鼠对G-CSF给药对骨肿瘤生长的影响具有抗性。这些数据表明G-CSF诱导的骨肿瘤生长刺激是OC依赖性的。
Inhibition of osteoclast (OC) activity has been associated with decreased tumor growth in bone in animal models. Increased recognition of factors that promote osteoclastic bone resorption in cancer patients led us to investigate whether increased OC activation could enhance tumor growth in bone. Granulocyte colony-stimulating factor (G-CSF) is used to treat chemotherapy-induced neutropenia, but is also associated with increased markers of OC activity and decreased bone mineral density (BMD). We used G-CSIF as a tool to investigate the impact of increased OC activity on tumor growth in 2 murine osteolytic tumor models. An 8-day course of G-CSF alone (without chemotherapy) significantly decreased BMD and increased OC perimeter along bone in mice. Mice administered G-CSF alone demonstrated significantly increased tumor growth in bone as quantitated by in vivo bioluminescence imaging and histologic bone marrow tumor analysis. Short-term administration of AMD3100, a CXCR4 inhibitor that mobilizes neutrophils with little effect on bone resorption, did not lead to increased tumor burden. However, OC-defective osteoprotegerin transgenic (OPG(Tg)) mice and bisphosphonate-treated mice were resistant to the effects of G-CSF administration upon bone tumor growth. These data demonstrate a G-CSF-induced stimulation of tumor growth in bone that is OC dependent.