Unraveling the contribution of ectoenzymes to myeloma life and survival in the bone marrow niche
Unraveling the contribution of ectoenzymes to myeloma life and survival in the bone marrow niche
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DOI：
10.1111/nyas.12485
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发表时间：
2015-01-01
期刊：
影响因子：
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通讯作者：
Malavasi, Fabio
中科院分区：
文献类型：
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作者：
Quarona, Valeria;Ferri, Valentina;Malavasi, Fabio
骨髓为产生大量细胞类型提供了受保护的环境。因此，骨骼是结构成分和可溶性因子的动态来源，这些成分和因子可以在本地使用，也可以在远离其生产地点的地方使用。我们讨论了胞外酶在人类骨髓瘤生长的骨龛中的作用。已经测试了选择的胞外酶促进参与信号传导、生长因子和激素合成以及免疫应答调节的底物产生的能力。由于同时跟踪所有这些活动很困难，我们将重点缩小到可能影响腺苷（ADO）合成的事件，腺苷是多种生物功能（包括局部免疫耐受性）的重要调节因子。我们的工作假设，将在本文中讨论和部分测试，是CD 38，和可能的BST 1/CD 157-两个NAD（+）消耗酶，在骨髓瘤生态位中是活跃的，并导致胞外酶的不连续链，其最终产物被肿瘤浆细胞利用作为其局部生存策略的一部分。辅助胞外酶包括PC-1/CD 203 a、CD 39和CD 73，它们控制ADO的产生。这里讨论的结果和正在进行的实验表明，骨髓瘤生态位主机的典型，以及替代，ADO生成的途径。其他的可能性提出和讨论。
The bone marrow provides a protected environment for generating a vast array of cell types. Bones are thus a dynamic source of structural components and soluble factors used either locally or at a distance from their site of production. We discuss the role of ectoenzymes in the bone niche where human myeloma grows. Selected ectoenzymes have been tested for their ability to promote production of substrates involved in signaling, synthesis of growth factors and hormones, and modulation of the immune response. Because of the difficulty of simultaneously tracking all these activities, we narrow our focus to events potentially influencing synthesis of adenosine (ADO), an important regulator of multiple biological functions, including local immunological tolerance. Our working hypothesis, to be discussed and partially tested herein, is that CD38, and likely BST1/CD157-both NAD(+)-consuming enzymes, are active in the myeloma niche and lead a discontinuous chain of ectoenzymes whose final products are exploited by the neoplastic plasma cell as part of its local survival strategy. Coadjuvant ectoenzymes include PC-1/CD203a, CD39, and CD73, which control the production of ADO. Results discussed here and from ongoing experiments indicate that the myeloma niche hosts the canonical, as well as alternative, pathways of ADO generation. Other possibilities are presented and discussed.