Bone marrow mesenchymal stem cells are abnormal in multiple myeloma
Bone marrow mesenchymal stem cells are abnormal in multiple myeloma
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DOI：
10.1038/sj.leu.2404621
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发表时间：
2007-05-01
期刊：
影响因子：
11.4
通讯作者：
Bourin, P.
中科院分区：
文献类型：
--
作者：
Corre, J.;Mahtouk, K.;Bourin, P.
最近的文献表明，肿瘤微环境的细胞也可能异常。为了解决这一假设在多发性骨髓瘤（MM），我们研究了骨髓间充质干细胞（BMMSCs），骨髓微环境中唯一的长寿细胞，基因表达谱和表型和功能研究在三组个人：MM患者，患者单克隆gamopathy的意义不明（MGUS）和健康的年龄匹配的主题。基因表达谱独立地将这些个体的BMMSC分为正常和MM组。MGUS BMMSC散布在这两组之间。在MM和正常BMMSC中差异表达的145个不同基因中，46%可能是肿瘤微环境串扰的原因。揭示了与MM病理生理特征有关的已知可溶性因子（即IL（白细胞介素）-6，DKK 1），并发现了参与血管生成、成骨分化或肿瘤生长的新因子。特别地，发现GDF 15诱导M0 LP-6（一种基质细胞依赖性骨髓瘤细胞系）的剂量依赖性生长。在功能上，MM BMMSCs诱导MOLP-6的过度生长，并且它们分化成成骨细胞谱系的能力受损。因此，MM BMMSC是异常的，并且可以产生非常有效的小生境以支持骨髓瘤细胞的存活和增殖。
Recent literature suggested that cells of the microenvironment of tumors could be abnormal as well. To address this hypothesis in multiple myeloma ( MM), we studied bone marrow mesenchymal stem cells (BMMSCs), the only long-lived cells of the bone marrow microenvironment, by gene expression profiling and phenotypic and functional studies in three groups of individuals: patients with MM, patients with monoclonal gamopathy of undefined significance (MGUS) and healthy age-matched subjects. Gene expression profile independently classified the BMMSCs of these individuals in a normal and in an MM group. MGUS BMMSCs were interspersed between these two groups. Among the 145 distinct genes differentially expressed in MM and normal BMMSCs, 46% may account for a tumor-microenvironment cross-talk. Known soluble factors implicated in MM pathophysiologic features (i.e. IL (interleukin)-6, DKK1) were revealed and new ones were found which are involved in angiogenesis, osteogenic differentiation or tumor growth. In particular, GDF15 was found to induce dose-dependent growth of MOLP-6, a stromal cell-dependent myeloma cell line. Functionally, MM BMMSCs induced an overgrowth of MOLP-6, and their capacity to differentiate into an osteoblastic lineage was impaired. Thus, MM BMMSCs are abnormal and could create a very efficient niche to support the survival and proliferation of the myeloma cells.