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Aspirin: A Regulator of Tumor Angiogenesis in Breast Cancer
Author(s) -
Maity Gargi,
Chakraborty Jinia,
Banerjee Snigdha,
Banerjee Sushanta K
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.775.17
Subject(s) - angiogenesis , matrigel , metastasis , neovascularization , cancer research , medicine , vascular permeability , cancer cell , cancer , endothelial stem cell , immunology , pathology , in vitro , chemistry , biochemistry
Background and Objective Tumor neovascularization / angiogenesisis a pathophysiological process in which new blood vessels are formed in the primary tumor site or distant organs to supply adequate nutrition to cancer cells for metastatic growth. Therefore, controlling tumor angiogenesis is an attractive target for cancer therapy. Structural abnormalities of vasculature (i.e. leakiness due to abnormal lining of pericytes on the microvessels) is 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 long term goal is to repurpose the drugs that may prevent tumor angiogenesis or normalize the vessels by repairing leakiness via recruiting pericytes or both. Our recent studies found that Aspirin (ASA)has the potency to inhibit breast cancer growth and metastasis, as well as reprogram the mesenchymal to epithelial transition (MET). Given the importance of ASA, we tested whether ASA may be able to regulate tumor angiogenesis. Methods We investigated the effect of low dose ASA (1mM, which is equivalent to 80mg human dose), ASA‐treated(2.5mM) conditioned media (231‐CM ASA ) or vehicle‐treated conditioned media (231‐CM VT ) of MDA‐MB‐231 cells on different endothelial cell physiology. These include endothelial cells' migration towards serum using modified Boyden chamber assay, in vitro capillary‐like structure formation on Matrigel, cell permeability using in vitro endothelial permeability assay and interactions of pericytes‐endothelial cells. We also determined the effect of ASA on various angiogenic factors associated with tumor angiogenesis. Finally, we determined the effect of ASA on invivo tumor angiogenesis using in vivo Angiogenesis Assay. Results and Conclusions We found that 231‐CM ASA significantly blocks in vitro migration, the formation of in vitro capillary‐like structures parallel with leakiness via incomplete interaction of pericytes and endothelial cells as compared to 231‐CM ASA . The antiangiogenic effect of ASA was also documented in in vivo assays. Mechanistically, ASA treatment blocks several angiogenic factors including VEGF‐A that are associated with these three events, implicating a low dose of Aspirin is potentially therapeutic for breast cancer via blocking and normalizing tumor angiogenesis. Support or Funding Information This work was supported by VA Merit Review Grants (S. Banerjee and S.K. Banerjee).