In an in vitro BBB model, breast cancer cells were found to secrete the proinflammatory neuropeptide Substance P (SP) that induces the secretion of tumor necrosis factor alpha (TNF-a) and angiopoietin-2 (Ang-2), leading to the redistribution of tight junction proteins ZO-1 and claudin-5 and resulting in an enhanced permeability of BE [46]. This evidence concerns the gene TNF and breast cancer.