Ethanol Enhances Estrogen Mediated Angiogenesis in Breast Cancer

Abstract

Angiogenesis, a highly regulated process, is exploited by tumors like breast cancer to ensure a constant supply of oxygen and nutrients and is key for tumor survival and progression. Estrogen and alcohol independently have been observed to contribute to angiogenesis in breast cancer but their combinatorial effects have never been evaluated. The exact mechanism by which estrogen and alcohol contribute to breast cancer angiogenesis remains to be elucidated. In this study, we defined the in vitro effects of the combination of estrogen and alcohol in breast cancer angiogenesis using the tubulogenesis and scratch wound assays. Conditioned media, generated by culturing the murine mammary cancer cell line, TG1-1, in estrogen and ethanol, enhanced tubule formation and migration as well as modulated the MAP Kinase pathway in the murine endothelial cell line, SVEC4-10. Additionally, estrogen and ethanol in combination enhanced the expression of the pro-angiogenic factors VEGF, MMP-9, and eNOS, and modulated Akt activation. These observations suggest that TG1-1 cells secrete pro-angiogenic molecules in response to the combination of estrogen and ethanol that modulate the morphological and migratory properties of endothelial cells. The data presented in this study, is the first in attempting to link the cooperative activity between estrogen and ethanol in breast cancer progression, underscoring correlations first made by epidemiological observations linking the two.

Pan-Cancer Analysis of NOS3 Identifies Its Expression and Clinical Relevance in Gastric Cancer

“…In BRCA, we also found that the higher expression of NOS3 mRNA was related to advanced tumor stage ( Supplementary Figure 4B ). These results were consistent with previous researches, which reported that NOS3 promoted angiogenesis and enhance the migration and invasion in breast cancer cells ( 11 – 13 ).…”

“…Another research in mesenchymal colorectal cancer patients reported that NOS3 upregulation occurs after Apc loss, which was associated with poor prognosis ( 10 ). In breast cancer, the increasing expression of NOS3 was reported to be a pro-angiogenic factor ( 11 ). It was found to promote angiogenesis via PI3K/Akt/mTOR pathway, and enhance the migration and invasion via NOS3-NO-sGC-cGMP signaling in breast cancer cells ( 12 , 13 ).…”

Bufalin inhibits peritoneal dissemination of gastric cancer through endothelial nitric oxide synthase‐mitogen‐activated protein kinases signaling pathway

“…Previous researches have reported that NOS3 was overexpressed in mesenchymal colorectal cancer, 32 breast cancer, 33 and related to poor prognosis. Our research initially reported that NOS3 overexpressed in GC tissues, and was an independent risk factor for poor prognosis in patients with GC.…”

Estrogens Regulate Placental Angiogenesis in Horses

“…Powazniak et al demonstrated that 17β-estradiol enhanced human endothelial cell proliferation, suggesting a promoting influence of 17βestradiol on angiogenesis [18]. Moreover, it has been shown that 17β-estradiol increases the migration of endothelial cells through binding to the estrogen receptors, leading to the formation of new vessels [2,19,20]. It has also been demonstrated that 17β-estradiol suppresses expression of the matrix metalloproteinase inhibitor in the mouse uterus, facilitating the cleavage of the extracellular matrix and the formation of new vessels [21].…”