Effect of endothelial-specific endorepellin expression on gene expression of breast cancer allografts in Tie2CreER;ERKi mice

To explore the translational implications of endorepellin in breast cancer, we created a double transgenic, inducible Tie2CreER;ERKi mouse line that expresses recombinant endorepellin specifically from the endothelium. We investigated the therapeutic effects of recombinant endorepellin overexpression in an orthotopic, syngeneic breast cancer allograft mouse model. Tamoxifen-induced expression of recombinant endorepellin specifically from the endothelium in Tie2CreER;ERKi mice markedly suppressed breast cancer allograft growth, hyaluronan deposition in the tumor proper and perivascular tissues, and tumor angiogenesis. To investigate the effects of endorepellin in the vasculature of triple-negative breast cancer in mice, we generated double transgenic mice expressing a tamoxifen-inducible endothelial-specific endorepellin knock-in gene, injected mice with either tamoxifen or control, and then injected syngeneic mouse breast cancer cells into the mammary fat pads. Breast tumor allografts were harvested at 22 days, RNA was extracted from tumor samples and sent for RNAseq analysis.