Aspirin suppresses tumor cell-induced angiogenesis and their incongruity.

Tumor neovascularization/tumor angiogenesis is a pathophysiological process in which new blood vessels are formed from existing blood vessels in the primary tumors to supply adequate oxygen and nutrition to cancer cells for their proliferation and metastatic growth to the distant organs. Therefore, controlling tumor angiogenesis is an attractive target for cancer therapy. Structural abnormalities of the vasculature (i.e., leakiness due to the abnormal lining of pericytes on the microvessels) are one of the critical features of tumor angiogenesis that sensitizes vascular cells to cytokines and helps circulating tumor cells to metastasize to distant organs. Our goal is to repurpose the drugs that may prevent tumor angiogenesis or normalize the vessels by repairing leakiness via recruiting pericytes or both. In this study, we tested whether aspirin (ASA), which could block primary tumor growth, regulates tumor angiogenesis. We investigated the effects of low (1 mM) and high (2.5 mM) doses of ASA (direct effect), and ASA-treated or untreated triple negative breast cancer (TNBC) cells' conditioned media (indirect effect) on endothelial cell physiology. These include in vitro migration using modified Boyden chamber assay, in vitro capillary-like structure formation on Matrigel, interactions of pericytes-endothelial cells and cell permeability using in vitro endothelial permeability assay. We also examined the effect of ASA on various molecular factors associated with tumor angiogenesis. Finally, we found the outcome of ASA treatment on in vivo tumor angiogenesis. We found that ASA-treatment (direct or indirect) significantly blocks in vitro migration and capillary-like structure formation by endothelial cells. Besides, we found that ASA recruits pericytes from multipotent stem cells and helps in binding with endothelial cells, which is a hallmark of normalization of blood vessels, and decreases in vitro permeability through endothelial cell layer. The antiangiogenic effect of ASA was also documented in vivo assays. Mechanistically, ASA treatment blocks several angiogenic factors that are associated with tumor angiogenesis, and suggesting ASA blocks paracrine-autocrine signaling network between tumor cells and endothelial cells. Collectively, these studies implicate aspirin with proper dose may provide potential therapeutic for breast cancer via blocking as well as normalizing tumor angiogenesis.

Racial disparity in breast cancer: can it be mattered for prognosis and therapy.

Breast cancer (BC) has emerged as a deadly disease that affects the lives of millions of women worldwide. It is the second leading cause of cancer-related deaths in the United States. Advancements in BC screening, preventive measures and treatment have resulted in significant decline in BC related deaths. However, unacceptable levels of racial disparity have been consistently reported, especially in African-American (AA) women compared to European American (EA). AA women go through worse prognosis, shorter survival time and higher mortality rates, despite higher cancer incidence reported in EA. These disparities are independent of socioeconomic status, access to healthcare or age, or even the stage of BC. Recent race-specific genetic and epigenetic studies have reported biological causes, which form the crux of this review. However, the developments are just the tip of the iceberg. Prioritizing primary research towards studying race-specific tumor microenvironment and biological composition of the host system in delineating the cause of these disparities is utmost necessary to ameliorate the disparity and design appropriate diagnosis/treatment regimen for AA women suffering from BC. In this review article, we discuss emerging trends and exciting discoveries that reveal how genetic/epigenetic circuitry contributed to racial disparity and discussed the strategies that may help in future therapeutic development.