Abstract
Neutrophil gelatinase-associated lipocalin (NGAL) has recently been identified in myeloperoxidase-negative neutrophil granules. Members of the lipocalin family are thought to bind and transport small lipophilic molecules such as retinoids and roles in cell regulation have been proposed. Recently, NGAL has also been demonstrated in the colonic mucosa in certain pathologic conditions.
The aim of this study was to examine the distribution of NGAL in normal and neoplastic tissues by immunohistochemistry. Interestingly, NGAL was found in a variety of normal and pathological human tissues. A cell type-specific pattern of expression was seen in bronchus, stomach, small intestine, pancreas, kidney, prostate gland, and thymus. The comparative analysis of the putative rat homologue neu-related lipocalin showed a very similar pattern of expression with the exception of pancreas and kidney. Neoplastic human tissues showed a very heterogeneous expression of NGAL protein. High NGAL levels were found in adenocarcinomas of lung, colon and pancreas. In contrast, renal cell carcinomas of various subtypes and prostate cancers contained low NGAL levels. Lymphomas and thymic tumours were negative for NGAL immuno-labeling. Knowledge about the location of NGAL in normal cells and in disease states provides the first clues towards understanding its biological function.
Similar content being viewed by others
References cited
Achen MG, Harms PJ, Thomas T, Richardson SJ, Wettenhall RE, Schreiber G (1992) Protein synthesis at the blood-brain barrier. The major protein secreted by amphibian choroid plexus is a lipocalin. J Biol Chem 267: 23170-23174.
Bartsch S, Tschesche H (1995) Cloning and expression of human neutrophil lipocalin cDNA derived from bone marrow and ovarian cancer cells. FEBS Lett 357: 255-259.
Borregaard N, Sehested M, Nielsen BS, Sengelov H, Kjeldsen L (1995) Biosynthesis of granule proteins in normal human bone marrow cells. Gelatinase is a marker of terminal neutrophil differentiation. Blood 85: 812-817.
Chu ST, Huang HL, Chen JM, Chen YH (1996) Demonstration of a glycoprotein derived from the 24p3 gene in mouse uterine luminal fluid. Biochem J 316: 545-550.
Cowland JB, Borregaard N (1997) Molecular characterization and pattern of tissue expression of the gene for neutrophil gelatinase-associated lipocalin from humans. Genomics 45: 17-23.
Flower DR (1996) The lipocalin protein family: structure and function. Biochem J 318: 1-14.
Garay-Rojas E, Harper M, Hraba-Renevey S, Kress M (1996) An apparent autocrine mechanism amplifies the dexamethasone-and retinoic acid-induced expression of mouse lipocalin-encoding gene 24p3. Gene 170: 173-180.
Glasgow BJ (1995) Tissue expression of lipocalins in human lacrimal and von Ebner's glands: colocalization with lysozyme. Graefes Archive for Clin Exp Ophthalmol 233: 513-522.
Hraba-Renevey S, Turler H, Kress M, Salomon C, Weil R (1989) SV40-induced expression of mouse gene 24p3 involves a post-transcriptional mechanism. Oncogene 4: 601-608.
Jones DE, Bevins CL (1992) Paneth cells of the human small intestine express an antimicrobial peptide gene. J Biol Chem 267: 23216-23225.
Kasik JW, Rice EJ (1995) An increase in expression of the lipocalin 24p3 is found in mouse uterus coincident with birth. Am J Obstet Gynecol 173: 613-617.
Liu Q, Nilsen-Hamilton M (1995) Identification of a new acute phase protein. J Biol Chem 270: 22565-22570.
Meheus LA, Fransen LM, Raymackers JG, Blockx HA, Van Beeumen JJ, Van Bun SM, Van de Voorde A (1993) Identification by microsequencing of lipopolysaccharide-induced proteins secreted by mouse macrophages. J Immunol 151: 1535-1547.
Nielsen BS, Borregaard N, Bundgaard JR, Timshel S, Sehested M, Kjeldsen L (1996) Induction of NGAL synthesis in epithelial cells of human colorectal neoplasia and inflammatory bowel diseases. Gut 38: 414-420.
Sengelov H, Boulay F, Kjeldsen L, Borregaard N (1994) Subcellular localization and translocation of the receptor for N-formylmethionyl-leucyl-phenylalanine in human neutrophils. Biochem J 299: 473-479.
Sodetz JM (1989) Structure and function of C8 in the membrane attack sequence of complement. Curr Topics Microbiol Immunol 140: 19-31.
Stoesz SP, Friedl A, Haag JD, Lindstrom MJ, Clark GM, Gould MN (1998) Heterogeneous expression of the lipocalin NGAL in primary breast cancers. Inte J Cancer 79: 565-572.
Stoesz SP, Gould MN (1995) Overexpression of neu-related lipocalin (NRL) in neu-initiated but not ras or chemically initiated rat mammary carcinomas. Oncogene 11: 2233-2241.
Treuheit M, Halsall HB (1992) Isolation of clobazam-orosomucoid complexes from patients' sera. Biomed Chromatogr 6: 50-52.
Venge P (1994) The monitoring of inflammation by specific cellular markers. Scand J Clin Lab Invest-Suppl 219: 47-54.
Xu SY, Pauksen K, Venge P (1995) Serum measurements of human neutrophil lipocalin (HNL) discriminate between acute bacterial and viral infections. Scand J Clin Lab Invest 55: 125-131.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Friedl, A., Stoesz, S., Buckley, P. et al. Neutrophil Gelatinase-associated Lipocalin in Normal and Neoplastic Human Tissues. Cell Type-specific Pattern of Expression. Histochem J 31, 433–441 (1999). https://doi.org/10.1023/A:1003708808934
Issue Date:
DOI: https://doi.org/10.1023/A:1003708808934