Epidemiological and biological evidence of neutrophil gelatinase-associated lipocalin (NGAL) in cancer.

Neutrophil gelatinase-associated lipocalin (NGAL), also known as lipocalin-2, is a 178-amino acid protein which exists in three molecular forms, including a 25-kDa monomer, a 45-kDa homodimer, and a 135-kDa heterodimer complexed with matrix metalloproteinase 9 (MMP-9). Polymorphonuclear neutrophils and tubular cells of the kidney are the most representative cellular sources. As such, NGAL is now considered the biochemical gold standard for early diagnosis of acute kidney injury. Recent evidence suggests, however, that ectopic or enhanced expression of NGAL may occur in many other pathologic conditions including cancer. Several epidemiologic studies, as reviewed in this chapter, showed that a variety of malignant tumors consistently overexpressed NGAL with increased concentration in blood, urine, and other biologic fluids. In addition, NGAL was frequently associated with tumor size, stage, and invasiveness. These features thus make it a potential biomarker for malignancy. A number of experimental studies also demonstrated that the ability to bind MMP-9, to scavenge iron into cancer cells along with the effect on subcellular localization of transmembrane proteins such as cadherins and catenins, confers this protein the potential to enhance cancer aggressiveness and makes it an appealing target of future anticancer research.