Myeloma cells (5TMM) and their interactions with the marrow marrow environment
Myeloma cells (5TMM) and their interactions with the marrow marrow environment
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DOI：
10.1016/j.bcmd.2004.04.012
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发表时间：
2004-09-01
影响因子：
2.3
通讯作者：
Vanderkerken, K
中科院分区：
文献类型：
--
作者：
Menu, E;Asosingh, K;Vanderkerken, K
骨髓瘤是一种致命的B细胞肿瘤，其特征是浆细胞的单克隆性增殖、骨溶解病变的发展和血管生成的诱导。骨髓瘤细胞主要分布在骨髓中，在那里它们接收到适当的生存和增殖信号。为了到达或扩散到骨髓，骨髓瘤细胞需要从骨髓的血管迁移到血管外腔。这一过程被称为“按喇叭”。在这篇综述中，将描述在5TMM模型中分析的寻的方案的步骤。这些小鼠模型起源于老年小鼠自发发展的骨髓瘤，此后通过向年轻同基因小鼠静脉注射骨髓瘤细胞进行繁殖。这些模型与人类的情况非常相似。本文报道的不同研究表明，5TMM细胞与骨髓内皮细胞的黏附部分由CD44v10介导，与基质细胞的黏附部分由CD44v6介导。5TMM细胞通过单核细胞趋化蛋白-1、层粘连蛋白-1和胰岛素样生长因子-1的作用向骨髓迁移。一旦穿过骨髓内皮细胞，它们就会通过分泌基质金属蛋白酶-9和尿激酶型纤溶酶原激活剂而侵入骨髓的血管外腔。当它们在骨髓中定居后，它们就会对IGF-1的影响变得敏感，IGF-1刺激细胞增殖并产生血管内皮生长因子。此外，针对骨髓和抑制剂的研究将得到强调。这些研究表明，5TMM模型对于揭示基本的生物学过程和确定新的治疗靶点是有用的。(C)2004 Elsevier Inc.保留所有权利。
Myeloma is a deadly B-cell neoplasm, characterized by the monoclonal proliferation of plasma cells, the development of osteolytic lesions, and the induction of angiogenesis. Myeloma cells are predominantly localized in the marrow where they receive the appropriate survival and proliferation signals. To reach or spread over the marrow, the myeloma cells need to migrate from the vascular to the extravascular compartment of the marrow. A process called "honling". In this review, the steps of the homing scheme, analyzed in the 5TMM model, will be described. These murine models originated from spontaneously developed myeloma in elderly mice and have since been propagated by intravenous injection of myeloma cells into young syngeneic mice. These models resemble the human condition closely. The different studies reported here demonstrate that adhesion of 5TMM cells to marrow endothelial cells is partially mediated by CD44v 10 and to stromal cells by CD44v6. The 5TMM cells migrate to the marrow through the effects of MCP-1, laminin-1, and IGF-1. Once past the marrow endothelium, they invade the extravascular compartment of the marrow by secreting MMP-9 and uPA. When they have settled in the marrow they become susceptible to the effects of IGF-1, which stimulates the cells to proliferate and produce VEGF. Furthermore, Studies targeting the marrow, with inhibitors will be highlighted. These studies show that the 5TMM models are useful for unraveling basic biological processes and for identifying new therapeutic targets. (C) 2004 Elsevier Inc. All rights reserved.