title: Lipocalin 2 performs contrasting, location-dependent roles in APCmin tumor initiation and progression.
abstract: Evidence that lipocalin 2 (LCN2) is oncogenic has grown in recent years and comes from both animal models and expression analysis from a variety of human cancers. In the intestine, LCN2 is overexpressed in colitis patients and its overexpression is a negative prognostic indicator in colorectal cancer. Functionally, LCN2 has a number of different activities that may contribute to its oncogenic potential, including increasing matrix metalloproteinase activity, control of iron availability and stimulating inflammation. In this report, we examined APCmin intestinal tumorigenesis in an LCN2-deficient background. We found that the loss of LCN2 increased tumor multiplicity specifically in the duodenum, suggesting a potential tumor-suppressive activity. Concurrently, however, LCN2 increased the average small intestinal tumor size particularly in the distal small intestine. We found that this increase was correlated to tumor iron(II) content, suggesting that an iron-scavenging role is important for LCN2 oncogenic activity in the intestine.
authors.affiliation: Division of Cellular and Molecular Research, National Cancer Centre Singapore, Singapore, Singapore.
authors.forename: P T
authors.initials: PT
authors.lastname: Reilly
authors.forename: W L
authors.initials: WL
authors.lastname: Teo
authors.forename: M J
authors.initials: MJ
authors.lastname: Low
authors.forename: A A
authors.initials: AA
authors.lastname: Amoyo-Brion
authors.forename: C
authors.initials: C
authors.lastname: Dominguez-Brauer
authors.forename: A J
authors.initials: AJ
authors.lastname: Elia
authors.forename: T
authors.initials: T
authors.lastname: Berger
authors.forename: G
authors.initials: G
authors.lastname: Greicius
authors.forename: S
authors.initials: S
authors.lastname: Pettersson
authors.forename: T W
authors.initials: TW
authors.lastname: Mak
mesh_terms: D000209:Acute-Phase Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D018450:Disease Progression; D005260:Female; D017491:Genes, APC; D007414:Intestinal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015513:Oncogene Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics
chemical_list: D000209:Acute-Phase Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; C071332:Lcn2 protein, mouse