Syndecan-1 and Metastasis Dormancy
Technical Report,01 Sep 2014,31 Aug 2015
University of Wisconsin-Madison, Madison United States
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The project focuses on the role of the local microenvironment on the escape of disseminated breast carcinoma cells from dormancy at the metastatic site and specifically, on the role that the cell surface heparan sulfate proteoglycan syndecan-1Sdc1 plays in these events. In a genetic model, we discovered that host Sdc1 is required for the efficient outgrowth of disseminated carcinoma cells into lung metastases. When analyzing the p38 pathway in mouse tissues, we found that this MAPK is activated in host lung tissue of Sdc1 KO mice compared to WT mice Aim 1. The development of an in vitro model to reconstitute the metastatic niche in the lung is ongoing. We are optimizing conditions to generate vascular structures and to grow lung endothelial cells, carcinoma cells and lung fibroblasts in 3D in microfluidic devices Aim 2. We have generatedSdc1loxlox mice and confirmed the correct location of loxP sites by adenoviral transduction of fibroblasts with Cre recombinase. Expression of Cre has been confirmed in Col1a2-Cre-ERT Cre driver mice by Western blot in TAM-treated fibroblasts andSdc1lox Col1a2-Cre-ERT heterozygous hybrids have been generated Aim 3.