Human breast cancer bone metastasis in vitro and in vivo: a novel 3D model system for studies of tumour cell-bone cell interactions
Human breast cancer bone metastasis in vitro and in vivo: a novel 3D model system for studies of tumour cell-bone cell interactions
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DOI：
10.1007/s10585-015-9737-y
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发表时间：
2015-10-01
影响因子：
4
通讯作者：
Ottewell, Penelope D.
中科院分区：
文献类型：
--
作者：
Holen, I.;Nutter, F.;Ottewell, Penelope D.
骨被确定为乳腺癌转移的优选部位。然而，造成这种偏好的确切机制仍然不明。为了改善晚期乳腺癌和骨骼受累患者的预后，我们需要更好地了解这一过程是如何启动和调节的。由于在患者中不易研究骨转移，研究人员迄今为止主要依赖于体内异种移植模型。这些方法的一个主要局限性是它们不含人骨微环境，而人骨微环境越来越被认为是转移瘤的重要组成部分。为了解决这一缺点，我们开发了一种新型的人源化骨模型，其中将1 x 10（5）表达荧光素酶的MDA-MB-231或T47 D人乳腺肿瘤细胞接种在体外活的人软骨下骨盘上。这些椎间盘在体外培养2周后含有功能性破骨细胞，并且在培养1周后呈阳性染色，表明骨吸收/形成活跃。体外接种MDA-MB-231或T47 D细胞定殖人骨芯，并保持存活，
Bone is established as the preferred site of breast cancer metastasis. However, the precise mechanisms responsible for this preference remain unidentified. In order to improve outcome for patients with advanced breast cancer and skeletal involvement, we need to better understand how this process is initiated and regulated. As bone metastasis cannot be easily studied in patients, researchers have to date mainly relied on in vivo xenograft models. A major limitation of these is that they do not contain a human bone microenvironment, increasingly considered to be an important component of metastases. In order to address this shortcoming, we have developed a novel humanised bone model, where 1 x 10(5) luciferase-expressing MDA-MB-231 or T47D human breast tumour cells are seeded on viable human subchaodral bone discs in vitro. These discs contain functional osteoclasts 2-weeks after in vitro culture and positive staining for calcine 1-week after culture demonstrating active bone resorption/formation. In vitro inoculation of MDA-MB-231 or T47D cells colonised human bone cores and remained viable for