Mechanical regulation of the microenvironmental niche in skin tumorigenesis

在一些实体癌中已经发现了控制肿瘤转移过程中组织趋向性的遗传因素，但遗传差异、肿瘤细胞之间的动态相互作用以及转移细胞的微环境--转移生态位--的贡献尚不清楚。对主要转移部位的微环境的分子特征表明，既有相似之处，也有明显的差异，这可能会影响不同类型癌症的定植。具体地说，肺转移和骨转移的交叉比较显示，有一些表达的基因是共同的，而另一些是不同的。但是，这些通路是否是肺和其他器官所特有的，还没有确定。同样，RNAseq和蛋白质组分析在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)中，与正常邻近组织相比，一致显示分泌的细胞外基质蛋白如纤维连接蛋白(FN)过表达。利用转基因小鼠，免疫细胞和基质细胞在转移部位建立了对创造“亲肿瘤”环境的贡献。这些细胞通过分泌ECM蛋白和其他细胞因子来协助肿瘤的定植。然而，转移灶的直接可视化在很大程度上是从组织病理学分析中观察到的，在时间上是离散的快照。需要的是建立转移的生态位的实时可视化，以了解为什么这些细胞能够在这些器官中定居。

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.