Basak Grzegorz Wladyslaw, Srivastava Anand S, Malhotra Rakesh, Carrier Ewa
Rebecca and John Moore's Cancer Center, University of California-San Diego, 3855 Health Science Drive, La Jolla, CA 92093-0960, USA.
Curr Pharm Biotechnol. 2009 Apr;10(3):345-6. doi: 10.2174/138920109787847493.
"Niche" is defined as a specialized regulatory microenvironment, consisting of components which control the fate specification of stem and progenitor cells, as well as maintaining their development by supplying the requisite factors. Bone marrow (BM) niche has a well-organized architecture and is composed of osteoblasts, osteoclasts, bone marrow endothelial cells, stromal cells, adipocytes and extracellular matrix proteins (ECM). These elements play an essential role in the survival, growth and differentiation of diverse lineages of blood cells, but also provide optimal growth environment for multiple hematological malignancies including multiple myeloma (MM). MM is a neoplastic plasma cell disorder which not only resides in BM but also converts it into specialized neoplastic niche. This niche aids the growth and spreading of tumor cells by a complex interplay of cytokines, chemokines, proteolytic enzymes and adhesion molecules. Moreover, the MM BM microenvironment was shown to confer survival and chemoresistance of MM cells to current therapies. However, our knowledge in this field is still in infancy and many details are unknown. Therefore, there is a strong need to further dissect the MM BM niche and understand the process of how the complex interactions with BM milieu influence MM growth, survival and development of resistance to chemotherapy. A better and more detailed understanding of neoplastic MM niche will provide a guiding model for identifying and validating novel targeted therapies directed against MM. Therefore, in the present review, we have focused principally on the basic features, physical structures, and functions of the BM niche and have highlighted its interaction with MM cells.
“生态位”被定义为一种特殊的调节性微环境,由控制干细胞和祖细胞命运特化的成分组成,并通过提供必要因子来维持它们的发育。骨髓(BM)生态位具有组织良好的结构,由成骨细胞、破骨细胞、骨髓内皮细胞、基质细胞、脂肪细胞和细胞外基质蛋白(ECM)组成。这些成分不仅在不同血细胞谱系的存活、生长和分化中起重要作用,还为包括多发性骨髓瘤(MM)在内的多种血液系统恶性肿瘤提供了最佳生长环境。MM是一种肿瘤性浆细胞疾病,它不仅存在于骨髓中,还将骨髓转化为特殊的肿瘤生态位。这个生态位通过细胞因子、趋化因子、蛋白水解酶和黏附分子的复杂相互作用促进肿瘤细胞的生长和扩散。此外,MM骨髓微环境被证明赋予MM细胞对当前疗法的存活能力和化疗耐药性。然而,我们在这个领域的知识仍处于起步阶段,许多细节尚不清楚。因此,迫切需要进一步剖析MM骨髓生态位,并了解与骨髓微环境的复杂相互作用如何影响MM的生长、存活和化疗耐药性发展的过程。对肿瘤性MM生态位有更好、更详细的了解将为识别和验证针对MM的新型靶向治疗提供指导模型。因此,在本综述中,我们主要关注了骨髓生态位的基本特征、物理结构和功能,并强调了它与MM细胞的相互作用。
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