Zipori Dov
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100 Israel.
Cancer Microenviron. 2010 Feb 5;3(1):15-28. doi: 10.1007/s12307-009-0034-7.
Multiple myeloma cells are reminiscent of hemopoietic stem cells in their strict dependence upon the bone marrow microenvironment. However, from all other points of view, multiple myeloma cells differ markedly from stem cells. The cells possess a mature phenotype and secrete antibodies, and have thus made the whole journey to maturity, while maintaining a tumor phenotype. Not much credence was given to the possibility that the bulk of plasma-like multiple myeloma tumor cells is generated from tumor-initiating cells. Although interleukin-6 is a major contributor to the formation of the tumor's microenvironment in multiple myeloma, it is not a major factor within hemopoietic stem cell niches. The bone marrow niche for myeloma cells includes the activity of inflammatory cytokines released through osteoclastogenesis. These permit maintenance of myeloma cells within the bone marrow. In contrast, osteoclastogenesis constitutes a signal that drives hemopoietic stem cells away from their bone marrow niches. The properties of the bone marrow microenvironment, which supports myeloma cell maintenance and proliferation, is therefore markedly different from the characteristics of the hemopoietic stem cell niche. Thus, multiple myeloma presents an example of a hemopoietic tumor microenvironment that does not resemble the corresponding stem cell renewal niche.
多发性骨髓瘤细胞在对骨髓微环境的严格依赖方面类似于造血干细胞。然而，从所有其他角度来看，多发性骨髓瘤细胞与干细胞明显不同。这些细胞具有成熟的表型并分泌抗体，因此在维持肿瘤表型的同时，已经完成了整个成熟过程。人们对大量浆细胞样多发性骨髓瘤肿瘤细胞由肿瘤起始细胞产生的可能性并未给予太多信任。尽管白细胞介素 -6 是多发性骨髓瘤肿瘤微环境形成的主要促成因素，但它并非造血干细胞龛内的主要因素。骨髓瘤细胞的骨髓龛包括通过破骨细胞生成释放的炎性细胞因子的活性。这些允许骨髓瘤细胞在骨髓内维持。相反，破骨细胞生成构成一种信号，驱使造血干细胞离开其骨髓龛。因此，支持骨髓瘤细胞维持和增殖的骨髓微环境的特性与造血干细胞龛的特征明显不同。因此，多发性骨髓瘤是一种造血肿瘤微环境不同于相应干细胞更新龛的例子。
