Lcn2, also known as lipocalin 2, is a secreted glycoprotein produced by immune cells like neutrophils and macrophages. It has diverse functions such as transporting hydrophobic ligands, regulating immune responses, maintaining iron balance, and fostering epithelial cell differentiation. It is involved in multiple physiological processes and its expression is upregulated in various human diseases and cancers [2].

In cancer cachexia, studies using Lcn2-knockout (KO) mouse models have revealed significant roles. In lung cancer cachexia, Lcn2 secreted by tissue-infiltrating neutrophils induces ferroptosis and wasting of adipose and muscle tissues. Inhibition of Lcn2 expression reduces cachexia symptoms and tissue wasting [1]. In pancreatic cancer cachexia, Lcn2 mediates adipocyte-muscle-tumor communication and hypothermia. Lcn2 deficiency in mice improves body temperature, and inhibits the loss of fat and muscle [3]. In sepsis-induced liver injury, Lcn2 depletion exacerbates liver injury, oxidative stress, and ferroptosis, while Lcn2 overexpression ameliorates LPS-induced cell injury in an in vitro sepsis model [4].

In conclusion, Lcn2 plays essential roles in various biological processes, especially in diseases like cancer cachexia and sepsis-induced liver injury. The use of Lcn2 KO mouse models has been crucial in uncovering its functions in these disease conditions, providing potential therapeutic targets for treatment.

References:

1. Wang, Dong, Li, Xiaohui, Jiao, Defeng, Zheng, Xiaohu, Wei, Haiming. 2023. LCN2 secreted by tissue-infiltrating neutrophils induces the ferroptosis and wasting of adipose and muscle tissues in lung cancer cachexia. In Journal of hematology & oncology, 16, 30. doi:10.1186/s13045-023-01429-1. https://pubmed.ncbi.nlm.nih.gov/36973755/

2. Bao, Yuxiang, Yan, Zhongliang, Shi, Nianmei, Cheng, Xiaoming, Lv, Junyuan. 2024. LCN2: Versatile players in breast cancer. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 171, 116091. doi:10.1016/j.biopha.2023.116091. https://pubmed.ncbi.nlm.nih.gov/38171248/

3. Lemecha, Mengistu, Chalise, Jaya Prakash, Takamuku, Yuki, Larson, Garrett, Itakura, Keiichi. 2022. Lcn2 mediates adipocyte-muscle-tumor communication and hypothermia in pancreatic cancer cachexia. In Molecular metabolism, 66, 101612. doi:10.1016/j.molmet.2022.101612. https://pubmed.ncbi.nlm.nih.gov/36243318/

4. Jiang, Yun, Jiang, Zhi-Tian, Zhao, Gang, Wang, Qian, Ling, Qi-Hua. 2024. LCN2 depletion aggravates sepsis-induced liver injury by regulating PTGS2-dependent ferroptosis. In International journal of medical sciences, 21, 2770-2780. doi:10.7150/ijms.98246. https://pubmed.ncbi.nlm.nih.gov/39512683/