title: Lipocalin-2-induced cytokine production enhances endometrial carcinoma cell survival and migration.
abstract: Lipocalin-2 (Lcn-2) is an acute-phase protein that has been implicated in diverse physiological processes in mice, including: apoptosis, ion transport, inflammation, cell survival, and tumorigenesis. This study characterized the biological activity of Lcn-2 in human endometrial carcinoma cells (RL95-2). Exposure of RL95-2 cells to Lcn-2 for >24 h reduced Lcn-2-induced cell apoptosis, changed the cell proliferation and up-regulated cytokine secretions, including: interleukin-8 (IL-8), inteleukin-6 (IL-6), monocyte chemotatic protein-1 (MCP-1) and growth-related oncogene (GRO). However, IL-8 mRNA and protein levels were dramatically increased in Lcn-2-treated RL95-2 cells. To determine the IL-8 effect on Lcn-2-treated RL95-2 cells was our major focus. Adding recombinant IL-8 (rIL-8) resulted in decreased caspase-3 activity in Lcn-2-treated cells, whereas the addition of IL-8 antibodies resulted in significantly increased caspase-3 activity and decreased cell migration. Data indicate that IL-8 plays a crucial role in the induction of cell migration. Interestingly, Lcn-2-induced cytokines, secretion from RL95-2 cells, could not show the potent cell migration ability with the exception of IL-8. We conclude that Lcn-2 triggered cytokine secretions to prevent RL95-2 cells from undergoing apoptosis and subsequently increased cell migration. We hypothesize that Lcn-2 increased cytokine secretion by RL95-2 cells, which in turn activated a cellular defense system. This study suggests that Lcn-2 may play a role in the human female reproductive system or in endometrial cancer.
authors.affiliation: Institute of Biochemical Science, College of Life Science, National Taiwan University, Taiwan.
authors.forename: Hsiu-Hsia
authors.initials: HH
authors.lastname: Lin
authors.forename: Chi-Jr
authors.initials: CJ
authors.lastname: Liao
authors.forename: Ying-Chu
authors.initials: YC
authors.lastname: Lee
authors.forename: Keng-Hsun
authors.initials: KH
authors.lastname: Hu
authors.forename: Hsien-Wei
authors.initials: HW
authors.lastname: Meng
authors.forename: Sin-Tak
authors.initials: ST
authors.lastname: Chu
mesh_terms: D000209:Acute-Phase Proteins / Q000494:pharmacology* / Q000502:physiology; D017209:Apoptosis; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000096:biosynthesis*; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism / Q000494:pharmacology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000494:pharmacology* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000494:pharmacology* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D017077:Culture Media, Conditioned; D016207:Cytokines; D016209:Interleukin-8; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D053148:Caspase 3