We showed that A7 significantly inhibited the growth of non-small cell lung adenocarcinoma in a xenograft mouse model. In this study, human BT474 HER2-amplified estrogen receptor positive breast cancer cells were injected into the mammary fat pad of athymic mice; tumors grew to approximately 200 mm3 prior to infusion with saline or 24 µg/kg/h A7 for 18 days. A marked reduction in tumor volume (5209 ± 419 mm3 to 1656 ± 124 mm3; n = 5, p < 0.05) and weight (3.6 ± 0.2 g to 2.2 ± 0.1 g; n = 5, p < 0.05) was observed in mice administered A7 as compared to saline control animals. Vessel density was decreased approximately 50% Selleck KU-60019 by the heptapeptide,

demonstating that A7 has antiangiogenic properties. Picrosirius red histochemistry showed that interstitial fibrosis (4.91 ± 0.96 percent/field versus 1.22 ± 0.19; n = 17–20, p < 0.0005) and perivascular fibrosis (49.32 ± 3.20 percent/vessel versus 13.35 ± 2.23; n = 20–21, p < 0.0001) were significantly reduced with A7 administration. This decrease in fibrosis was associated with a reduction in collagen I deposition, suggesting that A7 has an antifibrotic effect in breast cancer. Treatment with the heptapeptide

significantly decreased (31% reduction, n = 4, p < 0.05) selleck screening library the in vitro growth of cancer-associated fibroblasts (CAFs) isolated from orthotopic breast tumors

which could lead to a Fossariinae decrease in mitogenic factors and metalloproteinases produced by CAFs. A 2.3-fold increase in the mitogen-activated protein (MAP) kinase phosphatase DUSP1 was also observed, suggesting that the reduction in fibroblast proliferation may be due in part to inhibition of MAP kinase activity. Taken together, these data suggest that A7 may serve as a first-in-class chemotherapeutic agent for breast cancer targeting the tumor microenvironment through a reduction in angiogenesis and a decrease in CAF proliferation. O128 Angiotensin-(1–7) Inhibits VEGF and PlGF to Reduce Tumor Angiogenesis in Triple Negative Breast Cancer in an Orthotopic Mouse Model Patricia E. Gallagher 1 , David R. Soto-Pantoja1, Katherine Cook1, E. Ann Tallant1 1 Hypertension & Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA Triple negative breast tumors are aggressive, highly metastatic cancers that lack estrogen and progesterone receptors and have basal expression of the human epidermal growth factor receptor HER2. Angiotensin-(1–7) [A7], an endogenous heptapeptide hormone that activates the mas receptor, significantly reduced the in vivo proliferation of human triple negative breast tumor growth in an orthotopic model.