Targeting the Prometastatic Microenvironment of the Involuting Mammary Gland
Technical Report,01 Sep 2014,31 Aug 2015
New York University School of Medicine New York United States
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The hypothesis of this proposal is that Latent TGF-beta Binding Protein 1 LTBP1 is a pro-metastatic factor in breast cancer. To test this hypothesis we proposed three aims 1 Determine the utility of LTBP1 expression as a biomarker in human breast cancer 2 Determine the consequences of modulating LTBP1 levels on cell motility, invasion and metastasis in breast cancer cell lines 3 Investigate the pathobiological effects of gain and loss of LTBP1 in genetically engineered mouse models. Our most important findings in this cycle are that 1 elevated LTBP1 expression is associated with poor outcome in Basal and HER2 positive ER-negative breast cancers 2 highly metastatic variants breast cancer cells express elevated LTBP1 expression compared to parental lines 3 that high LTBP1S expression occurs in mesenchymal-like triple negative breast cancer cell lines and 4 that lowering expression level within these cells significantly reduces their invasive capability. This was achieved by determining the expression of total LTBP1 as well as LTBP1S and LTBP1Lisoforms by qPCR in a large panel of cells and their metastatic variants and by lentiviral knock down.