Accession Number : AD1000388


Title :   Syndecan-1 and Metastasis Dormancy


Descriptive Note : Technical Report,01 Sep 2014,31 Aug 2015


Corporate Author : University of Wisconsin-Madison, Madison United States


Personal Author(s) : Friedl,Andreas


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1000388.pdf


Report Date : 01 Sep 2015


Pagination or Media Count : 10


Abstract : 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-1(Sdc1) 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 generatedSdc1lox/lox 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-ER(T) Cre driver mice by Western blot in TAM-treated fibroblasts andSdc1lox/ Col1a2-Cre-ER(T) heterozygous hybrids have been generated (Aim 3).


Descriptors :   breast cancer , cancer research , metastasis , Dormancy , migration , lung , neoplasms


Distribution Statement : APPROVED FOR PUBLIC RELEASE