Development of Novel Molecularly Targeted Therapy to Secreted Frizzled-Related Protein 2 for Breast Cancer
Abstract
Most antiangiogenic drugs evaluated in breast cancer clinical trials inhibit angiogenesis by targeting the VEGFpathway. VEGF is a driver of tumor angiogenesis in breast cancer, however modest or negative phase III clinical resultssuggest further targets, pathways, or factors play a significant role. Furstenburger et al. evaluated VEGF expression in primarybreast cancers from patients and adjacent normal breast tissue and found no increase in VEGF levels. We hypothesized thatpro-angiogenesis factors other than VEGF are drivers of human breast cancer angiogenesis. To identify these proangiogenesisfactors, we developed a novel method of immuno-laser capture microdissection coupled with RNA amplificationand genome-wide gene expression to profile tumor vasculature cells from human breast tumors with comparison to normalbreast samples. In our analysis we identified that secreted frizzle-related protein 2 (SFRP2) mRNA levels were increased morethan 6-fold in breast cancer endothelium compared to normal vessels from benign breast tissue, and as shown byimmunohistochemistry 85% of breast tumors showed intense staining for SFRP2 in the neovasculature.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2020
- Accession Number
- AD1103061
Entities
People
- Ann-marie Broome
- Nancy Demore
Organizations
- Medical University of South Carolina