Mechanical regulation of the microenvironmental niche in skin tumorigenesis

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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.