多发性骨髓瘤患者MMP-9、MMP-2表达的研究

Studies of matrix metalloproteinase-9 and matrix metalloproteinase-2 expression in multiple myeloma patients

背景与目的:近年来的研究发现基质金属蛋白酶(MMPs)与骨重建、骨质重吸收和肿瘤浸润转移等过程有关。我们检测了多发性骨髓瘤(MM)患者的MMP-9和MMP-2水平,以探讨其与MM发病的关系和临床意义。方法:用酶联免疫吸附试验(ELISA)检测了30例MM患者单个核细胞培养液的MMP-9水平、24例MM患者骨髓基质细胞(BMSCs)培养液的MMP-2水平和12例对照组MMP-9、MMP-2水平。结果:19/30例进展期MM组的MMP-9表达水平显著高于11/30稳定期MM组和12例对照组(P<0.05);14/24例进展期MM组BMSCs的MMP-2表达水平显著高于10/24例稳定期MM组和对照组(P<0.05),稳定期MM组和对照组的MMP-9、MMP-2水平无显著差别(P>0.05);12例IgG型MM患者的MMP-9和血免疫球蛋白(M蛋白)水平呈正相关(r=0.87,P=0)。rIL-6(终浓度100ng/m l)、rIL-1β(终浓度10ng/m l)并不能显著改变BMSCs分泌的MMP-2,但9例进展期MM组BMSCs与人骨髓瘤细胞系U266细胞(终浓度2×105/mL)混合培养48小时后,MMP-2水平明显增高,显著高于上述进展期和稳定期MM患者和对照组的BMCSs(均为P<0.05)。结论:MMP-9、MMP-2水平升高与MM的病情进展有关;MMP-9可反映MM患者的肿瘤负荷,可能与MM的肿瘤浸润病理过程有关;而这些过程需骨髓瘤细胞和BMSCs相互作用而完成。

Background and purpose： Matrix Metalloproteinase （MMPs） are related to the process of bone rebuilding, bone resorption, tumor invasion and metastasis. We detected the level of MMP-9 and MMP-2 for multiple myeloma （MM） patients and tried to explore the role and clinical implications of these two proteins in MM. Methods： Expression of MMP-9 was detected in the culture fluid of mononuclear cells from 30 patients with MM and MMP-2 in the culture fluid of bone marrow stromal cells （BMSCs） from 24 patients with MM by ELISA. Results： The level of MMP-9 in 19/30 and MMP-2 in 14/24 patients with active MM were significantly higher than both the patients with stable MM （11/30 and 10/ 24） and 12 normal donors（ P 〈 0.05）, The levels of MMP-9 and MMP-2 in stable MM patients were not different from normal donors（P 〉0.05） Expression level of MMP-9 in 12 patients with the phenotype of secreting IgG was correlated to the level of M protein（ r = 0.87, P = 0 〈 0.05）. rlL-6 and rIL-1β did not play a role in stimulating MMP-2 secretion of BMSCs. When BMSCs from 9 patients with active MM were co-cultured with U266 cells （ human MM cell lines ）, there was a significant increase of MMP-2 in BMSCs （P 〈0.05）. Conclusions： The increase of MMPs is associated with disease progression. The level of MMP-9 is correlative to tumor burden and may have a role in the invasion and pathogenesis of MM. The interaction of myeloma cell and BMSCs is essential for the behavior of MM cells.