García-Sánchez Daniel, González-González Alberto, Alfonso-Fernández Ana, Del Dujo-Gutiérrez Mónica, Pérez-Campo Flor M
Department of Molecular Biology_IDIVAL, Faculty of Medicine, University of Cantabria, Santander 39011, Cantabria, Spain.
Servicio de Traumatología y Cirugía Ortopédica, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla (IDIVAL), Facultad de Medicina, Universidad de Cantabria, Santander 39008, Cantabria, Spain.
World J Stem Cells. 2023 May 26;15(5):421-437. doi: 10.4252/wjsc.v15.i5.421.
Multiple myeloma (MM) is a hematological malignancy characterized by the accumulation of immunoglobulin-secreting clonal plasma cells at the bone marrow (BM). The interaction between MM cells and the BM microenvironment, and specifically BM mesenchymal stem cells (BM-MSCs), has a key role in the pathophysiology of this disease. Multiple data support the idea that BM-MSCs not only enhance the proliferation and survival of MM cells but are also involved in the resistance of MM cells to certain drugs, aiding the progression of this hematological tumor. The relation of MM cells with the resident BM-MSCs is a two-way interaction. MM modulate the behavior of BM-MSCs altering their expression profile, proliferation rate, osteogenic potential, and expression of senescence markers. In turn, modified BM-MSCs can produce a set of cytokines that would modulate the BM microenvironment to favor disease progression. The interaction between MM cells and BM-MSCs can be mediated by the secretion of a variety of soluble factors and extracellular vesicles carrying microRNAs, long non-coding RNAs or other molecules. However, the communication between these two types of cells could also involve a direct physical interaction through adhesion molecules or tunneling nanotubes. Thus, understanding the way this communication works and developing strategies to interfere in the process, would preclude the expansion of the MM cells and might offer alternative treatments for this incurable disease.
多发性骨髓瘤（MM）是一种血液系统恶性肿瘤，其特征在于骨髓（BM）中分泌免疫球蛋白的克隆性浆细胞的积累。MM细胞与BM微环境之间的相互作用，特别是BM间充质干细胞（BM-MSCs），在这种疾病的病理生理学中起关键作用。多项数据支持这样的观点，即BM-MSCs不仅能增强MM细胞的增殖和存活，还参与MM细胞对某些药物的耐药性，促进这种血液肿瘤的进展。MM细胞与驻留的BM-MSCs之间的关系是一种双向相互作用。MM调节BM-MSCs的行为，改变其表达谱、增殖率、成骨潜能和衰老标志物的表达。反过来，经过修饰的BM-MSCs可以产生一组细胞因子，这些细胞因子会调节BM微环境以促进疾病进展。MM细胞与BM-MSCs之间的相互作用可以通过多种携带微小RNA、长链非编码RNA或其他分子的可溶性因子和细胞外囊泡的分泌来介导。然而，这两种类型细胞之间的通讯也可能涉及通过粘附分子或隧道纳米管的直接物理相互作用。因此，了解这种通讯的工作方式并制定干预该过程的策略，将阻止MM细胞的扩增，并可能为这种无法治愈的疾病提供替代治疗方法。
