Mesenchymal stem cells within tumour stroma promote breast cancer metastasis

Mesenchymal stem cells have been recently described to localize to breast carcinomas, where they integrate into the tumour-associated stroma. However, the involvement of mesenchymal stem cells (or their derivatives) in tumour pathophysiology has not been addressed. Here, we demonstrate that bone-marrow-derived human mesenchymal stem cells, when mixed with otherwise weakly metastatic human breast carcinoma cells, cause the cancer cells to increase their metastatic potency greatly when this cell mixture is introduced into a subcutaneous site and allowed to form a tumour xenograft. The breast cancer cells stimulate de novo secretion of the chemokine CCL5 (also called RANTES) from mesenchymal stem cells, which then acts in a paracrine fashion on the cancer cells to enhance their motility, invasion and metastasis. This enhanced metastatic ability is reversible and is dependent on CCL5 signalling through the chemokine receptor CCR5. Collectively, these data demonstrate that the tumour microenvironment facilitates metastatic spread by eliciting reversible changes in the phenotype of cancer cells.     

多范例自动需求建模和分析: 一种基于本体的方法

提出基于组织本体的问题领域描述, 用领域用户能够理解的术语与他们交互, 引导他们提供需求. 提出以问题领域描述为起点的多范例自动建模和分析方法, 提出组织结构的合理性, 组织目标的可实现性和组织过程的可行性等三个分析准则. 分析的结果可以进一步引导领域用户补充和修改问题领域描述, 分析完成后得到的问题领域模型可以作为前期需求文档, 为进一步的软件需求建模提供依据.