Targeting the Prometastatic Microenvironment of the Involuting Mammary Gland
Technical Report,01 Sep 2013,31 Aug 2017
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 are that1 elevated LTBP1 expression is associated with poor outcome in Basal and HER2 positive ER-negative breast cancers whereas other LTBP genes are more highly expressed in luminal cancers and associated with better outcome 2 LTBP1S is elevated in highly metastatic mesenchymal-like triple negative breast cancer cells which specific TGF-beta ligands and receptors and the LTBP binding partners Fibronectin and Fibrillin and 3 Knock down of LTBP1 in breast cancer cell line reduces cell invasion in transwell assays. 4 Metastatic mouse tumors C31-Tag and MMTV-PYMT express elevated LTBP1.
- Medicine and Medical Research