VEGF对多发性骨髓瘤骨髓基质细胞分泌IL-6的影响  

The influence of vascular endothelial growth factor on secretion of interleukin-6 of bone marrow stromal cells in multiple myeloma

作　　者：王晓波[1] 许咏青[2] 

机构地区：[1]大连医科大学附属二院血液内科,辽宁大连116027 [2]大连市儿童医院内科

出　　处：《中国实验诊断学》2008年第4期458-460,共3页Chinese Journal of Laboratory Diagnosis

摘　　要：目的研究血管内皮生长因子(VEGF)对多发性骨髓瘤患者骨髓基质细胞分泌白细胞介素6(IL-6)的影响,探讨多发性骨髓瘤(MM)的发病机制,为开发骨髓瘤新的治疗途径提供依据。方法骨髓来源于18例骨髓瘤患者,并取8例缺铁性贫血患者的骨髓做正常对照组。常规分离培养骨髓基质细胞(BMSCs),观察BMSCs生长情况,流式细胞仪检测BMSCs表型,取2-3代BMSCs进行实验,加入不同浓度外源性VEGF或作用不同时间,收集BMSCs上清液,以ELISA方法检测IL-6浓度。结果骨髓的基质细胞在体外成贴壁生长,为成纤维细胞形态,流式细胞仪检测其表型为CD54(+)、CD33(-)、CD31(-).骨髓瘤患者BMSCs分泌IL-6的结果高于正常对照BMSCs,两者差异有统计学意义(P<0.05)。不同浓度重组VEGF作用于骨髓瘤患者BMSCs或VEGF作用不同时间,均有显著刺激BMSCs分泌IL-6增多,呈现剂量和时间依赖性,P<0.05。结论在多发性骨髓瘤中,VEGF除了可以促进骨髓肿瘤血管的新生,支持瘤细胞的浸润转移,还可以明显刺激骨髓基质细胞分泌IL-6,促进肿瘤生长,针对VEGF的相关治疗将成为治疗骨髓瘤的新途径。Objective Through studying the effects of vascular endothelial growth factor（VEGF）on bone marrow stromal cells（BMSCs）,to focus on the secretion of interleukin-6（IL6）and to analyze the role of VEGF in the pathogenesis.Methods Bone marrow samples were obtained from 18patients.8 cases of Iron Deficiency Anemia（IDA） were served as normal control.MM patient and normal control BMSCs（MM BMSCs and N-BMSCs） were isolated and cultured routinely in vitro.For stimulation experiments,BMSCs were in passage 2 and 3.MM-BMSCs were stimulated with different concentrations of recombinant human VEGF or VEGF100μg/L for different time.ELISA was performed to detect the secretion of IL-6 in culture supernatants of BMSCs.Results Adherent BMSCs were mostly CD54 ＋ fibroblast-like cells.Notably,basal IL-6 concentrations in MM-BMSCs tended to be higher than in N-BMSCs,P〈0.05.IL-6 concentrations were determined in culture supernatants of MM-BMSCs after stimulation with different concentration VEGF or VEGF for different time.The VEGF induced a time-and dose-dependent increase in IL-6 secretion by MM-BMSCs.Analysis of significance for overall group differences was performed that indicated dose-and time-dependent increase in IL-6 secretion（P〈0.05）.Conclusion IL-6 and VEGF are very important cytokines in MM growth and infiltration.It is conceivable that the stromal cell compartment may,in response to angiogenic factors,release cytokines capable of sustaining tumor growth.The findings suggest that VEGF is a paracrine mediator supporting myeloma cell growth through the induction of IL-6 release by bone marrow stroma.

关 键 词：多发性骨髓瘤 基质细胞 血管内皮生长因子 白细胞介素6 

分 类 号：R733.3[医药卫生—肿瘤]