Targeting the Prometastatic Microenvironment of the Involuting mammary gland
Abstract
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 are1) we have confirmed in independent datasets that elevated LTBP1 expression is associated with poor outcome in Basal and HER2 positive ER-negative breast cancers; in contrast, LTBP 2-3 are more highly expressed in luminal cancers and associated with better outcome; 2) highly metastatic mesenchymal-like triple negative breast cancer cells express elevated LTBP1 and specific TGF-beta ligands and receptors and the LTBP binding partners Fibronectin and Fibrillin; and 4) that metastatic mouse tumors C3(1)-Tag and MMTV-PYMT express elevated LTBP1. This was achieved by determining the expression of total LTBP1 and binding partners by qPCR in a large panel of cells and their metastatic variants and by lentiviral knock down.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2016
- Accession Number
- AD1031101
Entities
People
- Pamela Cowin
Organizations
- Grossman School of Medicine