Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Old Road, Oxford, OX3 7LD, UK.
Cell Mol Life Sci. 2021 May;78(9):4085-4093. doi: 10.1007/s00018-021-03767-0. Epub 2021 Feb 11.
Multiple myeloma is a malignancy caused by the clonal expansion of abnormal plasma cells. Myeloma cells have proven to be incredibly successful at manipulating their microenvironment to promote growth and to evade modern therapies. They have evolved to utilise the integral signalling pathways of the bone and bone marrow to drive disease progression. The bone marrow is often described in the context of a single structure that fills the bone cavity and supports normal haematopoiesis. However, within that structure exists two anatomically different niches, the perivascular niche and the endosteal niche. These contain different cell types functioning to support normal immune and blood cell production as well as healthy bone. These cells secrete numerous signalling molecules that can influence myeloma cell biology and behaviour. The endosteal niche is home to specific bone cell lineages and plays a pivotal role in myeloma cell establishment and survival. This review will concentrate on some of the signalling pathways that are hijacked by myeloma cells to shape a favourable environment, and the different influences myeloma cells are exposed to depending on their spatial location within the bone marrow.
多发性骨髓瘤是一种由异常浆细胞克隆性扩增引起的恶性肿瘤。骨髓瘤细胞已经被证明非常善于操纵其微环境，以促进生长并逃避现代疗法。它们已经进化到利用骨骼和骨髓的完整信号通路来驱动疾病进展。骨髓通常被描述为充满骨腔并支持正常造血的单一结构。然而，在这个结构中存在两个解剖上不同的龛位，即血管周龛位和骨内膜龛位。这些龛位包含不同的细胞类型，它们的功能是支持正常的免疫和血细胞生成以及健康的骨骼。这些细胞分泌许多信号分子，这些信号分子可以影响骨髓瘤细胞的生物学和行为。骨内膜龛位是特定的骨细胞谱系的所在地，在骨髓瘤细胞的建立和存活中起着关键作用。本综述将集中讨论骨髓瘤细胞劫持的一些信号通路，这些信号通路塑造了一个有利的环境，以及骨髓瘤细胞根据其在骨髓中的空间位置而受到的不同影响。
