Int J Biol Sci 2011; 7(1):74-86. doi:10.7150/ijbs.7.74

Research Paper

Lipocalin-2-induced cytokine production enhances endometrial carcinoma cell survival and migration

Hsiu-Hsia Lin1,3, Chi-Jr Liao1, Ying-Chu Lee2, Keng-Hsun Hu2, Hsien-Wei Meng2, Sin-Tak Chu1,2

1. Institute of Biochemical Science, College of Life Science, National Taiwan University, Taiwan;
2. Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan;
3. Department of Internal Medicine, National Taiwan University Hospital, Taiwan.

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Lin HH, Liao CJr, Lee YC, Hu KH, Meng HW, Chu ST. Lipocalin-2-induced cytokine production enhances endometrial carcinoma cell survival and migration. Int J Biol Sci 2011; 7(1):74-86. doi:10.7150/ijbs.7.74. Available from

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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.

Keywords: apoptosis, cytokine secretion, cellular defense, endometrial carcinoma cells