Role of oncogene 24p3 neutrophil gelatinase-associated lipocalin (NGAL) in digestive system cancers

Abstract

Neutrophil gelatinase-associated lipocalin, known also as 24p3 lipocalin, lipocalin-2 or uterocalin (in mouse), is a small secretory protein binding small molecular weight ligands which takes part in numerous processes including apoptosis induction in leukocytes, iron transport, smell, and prostaglandins and retinol transport [19]. It was discovered in activated neutrophils as a covalent peptide associated with human gelatinase neutrophils [7]. Neutrophil lipocalin is secreted physiologically in the digestive system, respiratory tract, renal tubular cells, liver or immunity system. Systematic (circulated in plasma) neutrophil gelatinase come from multiple sources; it may be synthesized in the liver, secreted from activated neutrophils or macrophages, or derive from atherosclerosis or inflammatory endothelial cells [17]. NGAL is stored secondarily in granulates with lactoferrin, calprotectin or MAC-1, which take part in neutrophils' action and migration [13,19]. NGAL participates in acute and chronic inflammation (production of NGAL is indicated by factors conducive to cancer progression) [13,21]. NGAL levels increase in inflammatory or endothelial damage. NGAL level is measured in blood or urine. It is known as a kidney failure factor [7,20]. NGAL is therefore one of the most promising new generation biomarkers in clinical nephrology [6]. The role of NGAL in digestive system neoplasms has not been explored in detail. However, overexpression of this marker was proved in neoplasms such as esophageal carcinoma, stomach cancer, pancreatic cancer or colon cancer, which may indicate an association between concentration and neoplasm [3].

Downregulation of NGAL is Required for the Inhibition of Proliferation and the Promotion of Apoptosis of Human Gastric Cancer MGC-803 Cells

“…Similarly, Michalak et al supported that NGAL has been considered to be an oncogene in gastric cancer, and high expression of NGAL was also observed in gastric cancer. It seemed that the intensity of its over-expression was linked to neoplasm [20]. Additionally, it has been found that urine NGAL is significantly increased and related to the degree of albuminuria in type 2 diabetic nephropathy (T2DN) [21].…”

The Postoperative Plasmatic Level of Neutrophil Gelatinase-associated Lipocalin Does not Reflect its Tissue Expression in Critically ill Patients with High Abdominal Pressure

“…In all of the cases, the clinical and laborator y investigations were performed from the first 24 h following surgery. The abdominal pressure was invasively evaluated NGAL was firstly described as being a matrix protein released from the granules of activated neutrophils [1][2][3][4]. It was later observed that NGAL can be also derived at the glomerular endothelial/mesangial cells, freely filtered through the glomerular membrane and reabsorbed by endocytosis in the proximal tubule [6].…”