Antibodies for NADPH oxidase (NOX) family proteins
Reactive oxygen species (ROS) are regulators of endothelial cell migration, proliferation, and survival, all of which are critically involved in angiogenesis associated with malignant neoplasms. The primary role of the NADPH oxidase (NOX) family of proteins, consisting of seven members (NOX1-5 and DUOX1-2), is to generate ROS, in particular superoxide or H2O2. Several of these transmembrane oxidases are expressed in cells of the tumor microenvironment. The NOX1, -2, and -4 isoforms were demonstrated to be present in an assortment of tumor cell types, while endothelial cells express NOX1, -2, -4, and -5. Importantly, the NOX1-4 enzymes each form distinct multiprotein complexes with a set of regulatory proteins that are required for catalytic activation as well as enzyme localization and stability, including p22phox, p40phox, p47phox, p67phox, and Rac. NOX-generated ROS promote angiogenesis in multiple ways in cancer cells and tumor-associated endothelial cells. In addition to stimulating autocrine tumor cell proliferation, tumor cell-derived ROS can also drive angiogenesis in nearby endothelial cells by triggering the release of paracrine growth factors like VEGF. ROS also control the upregulation of key pro-angiogenic factors such as HIF-1 and matrix metalloproteinases (MMPs). As noted above, ROS produced by tumor-associated endothelial cells leads to their proliferation and increased motility. Because of the major impact that NOX family proteins have on cancer-related angiogenesis, we would like to use this issue of the GeneTex Cancer Biology Newsletter to introduce some of the GeneTex products useful for the study of NADPH oxidases and their regulatory proteins.