Accession Number:

AD1103061

Title:

Development of Novel Molecularly Targeted Therapy to Secreted Frizzled-Related Protein 2 for Breast Cancer

Descriptive Note:

Technical Report,01 Mar 2019,28 Feb 2020

Corporate Author:

Medical University of South Carolina Charleston United States

Personal Author(s):

Report Date:

2020-03-01

Pagination or Media Count:

12.0

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.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE