Apoptosis, angiogenesis, inflammation, and oxidative stress: basic interactions in patients with early and metastatic breast cancer

Breast cancer (BC) is a complex, multi-stage disease involving deregulation of different signaling cascades. The present study was conducted to determine the extent of apoptosis, angiogenesis, inflammation, and oxidative stress in patients with different stages of BC as an approach to disease biological behavior. Therefore, plasma levels of soluble (s) Fas, bcl-2 as antiapoptotic indices; interleukin (IL)-8, tumor necrosis factor (TNF)-alpha as apoptotic, inflammatory, angiogenic indices; lipid peroxides (LPO), nitric oxide (NO) as oxidative stress and angiogenic indices were measured in patients with BC. Thirty-seven newly diagnosed patients with BC, 30 patients with benign breast masses, and 30 healthy controls were recruited. Plasma levels of sFas, bcl-2, IL-8, and TNF-alpha were measured by immunosorbent assay kits and LPO and NO by chemical methods. Plasma sFas and LPO were significantly higher in BC patients versus benign breast masses and healthy controls ( < 0.0001). Bcl-2, IL-8, TNF-alpha, and NO were significantly higher in benign breast masses ( < 0.0001, < 0.037, < 0.0001, < 0.001) and BC ( < 0.0001) versus controls and in BC versus benign breast masses ( < 0.0001). sFas, bcl-2, IL-8, TNF-alpha, LPO, and NO were increased with advanced tumor stages. There were positive correlations between sFas, bcl-2, IL-8 TNF-alpha, LPO, and NO. BC tumor cells overexpress bcl-2 and sFas to secure their outgrowth and survival. However, this coincides with activation of physiologic regulatory mechanisms, as increased IL-8, TNF-alpha, LPO, and NO, which try to stop tumor cells by inducing apoptosis. Outcompeting of these mechanisms result in tumor progression as IL-8, TNF-alpha, and NO are also angiogenic stimulators.