Mechanical regulation of the microenvironmental niche in skin tumorigenesis

在肿瘤转移中控制组织嗜性的遗传因素已经被确定 在一些实体癌中，但是遗传差异的贡献， 肿瘤细胞之间的相互作用和转移细胞的微环境- “转移性小生境”还没有被很好地理解。分子表征 从转移的主要部位的微环境表明既相似又不同 差异，这可能会影响不同类型癌症的定植。具体地说， 肺转移与骨转移的交叉比较显示， 有共同点，而另一些则不同。但是，这些途径是否是肺特有的， 与其他器官的对比还没有确定。类似地，RNAseq和蛋白质组学分析 不同组织来源的实体原发癌，如乳腺癌、喉癌、尿路上皮癌和 非小细胞肺癌与正常邻近组织相比， 分泌的细胞外基质蛋白如纤连蛋白（FN）的过表达。使用 转基因小鼠，免疫和基质细胞对创造 已经在转移部位建立了“促肿瘤”环境。这些细胞帮助 通过分泌ECM蛋白和其它细胞因子来促进肿瘤定殖。然而，直接 从组织病理学上观察到转移灶的可视化 分析为时间上的离散快照。所需要的是实时可视化的 建立转移小生境，以了解为什么这些细胞能够在这些细胞中定植， 机关

The genetic factors governing tissue tropism in cancer metastasis have been identified in some solid cancers, but the contributions of the genetic differences, the dynamic interactions between tumor cells, and the microenvironment of the metastasizing cells- the "metastatic niche" are not well understood. Molecular characterization of the microenvironments from the major sites of metastases indicates both similarities and distinct differences, which may influence colonization across types of cancers. Specifically, cross-comparison of lung versus bone metastases revealed that there were some expressed genes in common whereas others were distinct. But, whether these pathways are specific to lung versus other organs have not been identified. Similarly, RNAseq and proteomic analysis across solid primary carcinomas of different tissue origins such as breast, laryngeal, urothelial and non- small cell lung cancers when compared to normal adjacent tissue consistently show an overexpression of secreted extracellular matrix proteins such as fibronectin (FN) . Using genetically modified mice, the contributions of the immune and stromal cells towards creating a "pro-tumor" environment have been established at sites of metastasis. These cells assist tumor colonization by secreting ECM proteins and other cytokines. However, direct visualization of the metastatic niche has largely been observed from histopathological analysis as discrete snapshots in time. What is needed is the real-time visualization of the establishment of the metastatic niche to understand why these cells are able to colonize these organs.