Development of Novel Molecularly Targeted Therapy to Secreted Frizzled-Related Protein 2 for Breast Cancer
Technical Report,01 Mar 2019,28 Feb 2020
Medical University of South Carolina Charleston United States
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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.
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