多发性骨髓瘤患者OPN、CD44v_6的表达与病情进展的关系

Relationship of expression of osteopontin and CD44 variant isoforms in multiple myeloma patients with progress of multiple myeloma

背景与目的:骨桥蛋白(osteopontin,OPN)与其受体——CD44受体和整合素受体结合后,参与骨重建、骨质重吸收、血管重塑、癌细胞浸润和转移等过程。为此本研究检测了多发性骨髓瘤(multiple myeloma,MM)患者的OPN和变异的CD44受体(CD44v6)水平,以探讨其与MM病情进展的关系。方法:32例MM患者,分为A组(包括初发和复发病例)和B组(化疗后病情稳定)2组,同时收集外伤骨折或非肿瘤良性贫血患者15例作为对照。采用酶链免疫吸附试验(ELISA)分别检测了MM患者和对照组的单个核细胞及骨髓基质细胞(bone marrow mononuclear cells,BMSCs)培养上清液的OPN、CD44v6水平并进行相关分析。结果:A组(19例)患者的OPN表达水平显著高于B组(13例)和对照组患者(P<0.05)。对A组中的14例患者和B组中的10例患者进行了CD44v6水平检测,其结果A组的CD44v6表达水平显著高于B组和对照组患者(P<0.05),B组的CD44v6水平显著高于对照组(P<0.05);OPN水平与CD44v6(r=0.52,P=0.000)、恶性浆细胞数(r=0.74,P=0.000)、M蛋白水平(r=0.53,P=0.014)、血β2-MG水平(r=0.62,P=0.002)均呈正相关。结论:OPN和CD44v6水平升高与MM的发生和病情进展有关;可能与MM的肿瘤负荷、疾病阶段和肿瘤浸润有关。

Background and purpose： Osteopontin （OPN） is a glycophosphoprotein that is expressed by numerous human cancer cells. The function of OPN in skeletal modeling and remodeling, bone resorption, angiogenesis and tumor cell metastasis and progression through binding with integrin and CD44 receptors were studied. Our purpose of the study was to detect the level of osteopontin（OPN） and CD44 variant isoforms（CD44v6） in multiple myeloma （MM） patients, and to explore the relationship between OPN and CD44v6 with the progress of MM. Methods： 32 MM patients were admitted to our hospital from Sep. 2007 to Dec. 2008. The patients were divided into two groups, group A （untreated and relapsed MM patients） and B （stable MM patients）, and the control group including 15 subjects were the benign anemia patients or healthy people who suffered bone fracture. Bone marrow mononuclear cells （MNCs） and bone marrow stromal cells （BMSCs） from MM patients and subjects were investigated as potential OPN and CD44v6 producers. The level of OPN and CD44v6 of the conditioned media from MM patients and subjects were analyzed by ELISA. Results： The OPN level in group A （19 cases） was significantly higher than group B （13 cases） and control group （P〈0.05）. The CD44v6 level of 14 patients in group A was significantly higher than that of 10 cases in group B and control group （P〈0.05）; The OPN level of MM patients was correlated with the level of CD44v6 （r=0.52, P=0.O00）, the percentage of plasma cells in the bone marrow （r=0.74, P=0.000）, M protein （r=0.53, P=0.014）, and β2-microglubin （r=0.62, P=0.002）. Conclusion： The increase of OPN and CD44v6 is associated with progress and pathogenesis of MM, and may be involved with tumor burden, stage and tumor invasion.