Multiple Myeloma Bone Marrow Niche

被引:68
作者
Basak, Grzegorz Wladyslaw [1 ,2 ]
Srivastava, Anand S. [3 ]
Malhotra, Rakesh [4 ,5 ]
Carrier, Ewa [1 ]
机构
[1] Univ Calif San Diego, Rebecca & John Moores Canc Ctr, San Diego, CA 92103 USA
[2] Med Univ Warsaw, Dept Hematol Oncol & Internal Dis, Warsaw, Poland
[3] Salk Inst Biol Studies, Dept Stem Cell, La Jolla, CA 92037 USA
[4] Univ Calif San Diego, Dept Nephrol, La Jolla, CA 92093 USA
[5] San Diego State Univ, Sch Publ Hlth, San Diego, CA 92182 USA
关键词
Multiple myeloma; microenvironment; niche; bone marrow; MEDIATED DRUG-RESISTANCE; FACTOR-KAPPA-B; HEPATOCYTE GROWTH-FACTOR; MESENCHYMAL STEM-CELLS; UROKINASE PLASMINOGEN-ACTIVATOR; INFLAMMATORY PROTEIN 1-ALPHA; NECROSIS-FACTOR-ALPHA; ENDOTHELIAL-CELLS; OSTEOCLAST FORMATION; RECEPTOR ACTIVATOR;
D O I
10.2174/138920109787847493
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
"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.
引用
收藏
页码:335 / 346
页数:12
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