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Increased Expression of Extracellular Matrix Metalloproteinase Inducer (CD147) in Multiple Myeloma: Role in Regulation of Myeloma Cell Proliferation

机译：多发性骨髓瘤中细胞外基质金属蛋白酶诱导剂（CD147）的表达增加：在骨髓瘤细胞增殖调控中的作用

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摘要

Multiple myeloma (MM) is preceded by the asymptomatic premalignant state, monoclonal gammopathy of undetermined significance (MGUS). Although MGUS patients may remain stable for years, they are at increased risk of progressing to MM. A better understanding of the relevant molecular changes underlying the transition from an asymptomatic to symptomatic disease state is urgently needed. Our studies show for the first time that the CD147 molecule (extracellular matrix metalloproteinase inducer) may be playing an important biological role in MM. We first demonstrate that CD147 is over-expressed in MM plasma cells (PCs) vs. normal and premalignant PCs. Next, functional studies revealed that the natural CD147 ligand, cyclophilin B, stimulates MM cell growth. Moreover, when MM patient PCs displaying bimodal CD147 expression were separated into CD147bright and CD147dim populations and analyzed for proliferation potential, we discovered that CD147bright PCs displayed significantly higher levels of cell proliferation than did CD147dim PCs. Lastly, CD147 silencing significantly attenuated MM cell proliferation. Taken together, these data suggest that the CD147 molecule plays a key role in MM cell proliferation and may serve as an attractive target for reducing the proliferative compartment of this disease.
机译：在未经形成的骨髓瘤（MM）之前，多种骨髓瘤（MM），单克隆血管病的未确定意义（MGU）。虽然MGUS患者多年来可能保持稳定，但它们的进展情况增加到mm。迫切需要更好地理解从无症状到症状疾病状态的过渡到症状的相关分子变化。我们的研究表明CD147分子（细胞外基质金属蛋白酶诱导剂）首次表现为MM的重要生物学作用。我们首先证明CD147在MM等离子体细胞（PCS）与正常和预先进行的PC中过于表达。接下来，功能性研究表明，天然CD147配体，环托酚B，刺激MM细胞生长。此外，当显示双峰CD147表达的MM患者PC分离成CD147 亮℃和CD147 dim 群体，并分析增殖潜力，我们发现CD147 Bright PC显示比CD147 DIM PC显着更高水平的细胞增殖。最后，CD147沉默显着减弱MM细胞增殖。总之，这些数据表明CD147分子在MM细胞增殖中起关键作用，可用作减少该疾病增殖舱的有吸引力的靶标。

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