Adipose, Bone, and Myeloma: Contributions from the Microenvironment.
Adipose, Bone, and Myeloma: Contributions from the Microenvironment.
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DOI：
10.1007/s00223-016-0162-2
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发表时间：
2017-05
影响因子：
4.2
通讯作者：
Reagan MR
中科院分区：
文献类型：
--
作者：
McDonald MM;Fairfield H;Falank C;Reagan MR
全球的研究人员正在努力寻找治疗多发性骨髓瘤（MM）的方法，MM是一种破坏性的血癌，全球每年约有75万人被诊断出。虽然MM靶向多个器官系统，但超过90%的患者经历的破坏性骨骼破坏通常最严重地影响患者的发病率、疼痛和生活质量。因此，预防骨骼疾病是MM治疗的优先事项，了解骨髓瘤细胞如何以及为什么靶向骨髓（BM）是这一过程的基础。本文综述重点关注多发性骨髓瘤研究的一个关键领域：骨骼微环境对疾病起源、进展和耐药性的贡献。我们描述了BM龛中的一些关键细胞类型：破骨细胞、成骨细胞、骨细胞、脂肪细胞和间充质干细胞。然后，我们专注于这些关键的细胞参与者是如何或可能是如何调节一系列疾病相关的过程，包括MM生长，耐药性和骨骼疾病（包括骨质溶解，骨折和高钙血症）。我们总结了有关MM-骨细胞和MM-脂肪细胞关系以及MM细胞随后的表型变化或适应性的文献，旨在更深入地了解骨髓瘤细胞如何在骨骼中生长导致骨破坏。我们确定了干预这些网络的途径和疗法，以阻止肿瘤生长和/或诱导骨再生。总的来说，我们的目标是说明新的治疗靶分子，蛋白质和细胞介质如何提供新的途径来攻击这种疾病，同时审查目前使用的疗法。
Researchers globally are working towards finding a cure for multiple myeloma (MM), a destructive blood cancer diagnosed yearly in ~750,000 people worldwide. Although MM targets multiple organ systems, it is the devastating skeletal destruction experienced by over 90% of patients that often most severely impacts patient morbidity, pain, and quality of life. Preventing bone disease is therefore a priority in MM treatment, and understanding how and why myeloma cells target the bone marrow (BM) is fundamental to this process. This review focuses on a key area of MM research: the contributions of the bone microenvironment to disease origins, progression, and drug resistance. We describe some of the key cell types in the BM niche: osteoclasts, osteoblasts, osteocytes, adipocytes and mesenchymal stem cells. We then focus on how these key cellular players are, or could be, regulating a range of disease-related processes spanning MM growth, drug resistance, and bone disease (including osteolysis, fracture, and hypercalcemia). We summarize the literature regarding MM-bone cell and MM-adipocyte relationships and subsequent phenotypic changes or adaptations in MM cells, with the aim of providing a deeper understanding of how myeloma cells grow in the skeleton to cause bone destruction. We identify avenues and therapies that intervene in these networks to stop tumor growth and/or induce bone regeneration. Overall, we aim to illustrate how novel therapeutic target molecules, proteins, and cellular mediators may offer new avenues to attack this disease while reviewing currently utilized therapies.