title: Lactoferrin deficiency promotes colitis-associated colorectal dysplasia in mice.
abstract: Nonresolving inflammatory processes affect all stages of carcinogenesis. Lactoferrin, a member of the transferrin family, is involved in the innate immune response and anti-inflammatory, anti-microbial, and anti-tumor activities. We previously found that lactoferrin is significantly down-regulated in specimens of nasopharyngeal carcinoma (NPC) and negatively associated with tumor progression, metastasis, and prognosis of patients with NPC. Additionally, lactoferrin expression levels are decreased in colorectal cancer as compared with normal tissue. Lactoferrin levels are also increased in the various phases of inflammation and dysplasia in an azoxymethane-dextran sulfate sodium (AOM-DSS) model of colitis-associated colon cancer (CAC). We thus hypothesized that the anti-inflammatory function of lactoferrin may contribute to its anti-tumor activity. Here we generated a new Lactoferrin knockout mouse model in which the mice are fertile, develop normally, and display no gross morphological abnormalities. We then challenged these mice with chemically induced intestinal inflammation to investigate the role of lactoferrin in inflammation and cancer development. Lactoferrin knockout mice demonstrated a great susceptibility to inflammation-induced colorectal dysplasia, and this characteristic may be related to inhibition of NF-κB and AKT/mTOR signaling as well as regulation of cell apoptosis and proliferation. Our results suggest that the protective roles of lactoferrin in colorectal mucosal immunity and inflammation-related malignant transformation, along with a deficiency in certain components of the innate immune system, may lead to serious consequences under conditions of inflammatory insult.
authors: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, Cancer Research Institute, Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan, China.
authors: Qiurong
authors: Q
authors: Ye
authors: Center for Medical Research, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Ying
authors: Y
authors: Zheng
authors: Department of Pathology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Songqing
authors: S
authors: Fan
authors: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, Cancer Research Institute, Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan, China.
authors: Zailong
authors: Z
authors: Qin
authors: Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Nan
authors: N
authors: Li
authors: Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Anliu
authors: A
authors: Tang
authors: Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Feiyan
authors: F
authors: Ai
authors: Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Xuemei
authors: X
authors: Zhang
authors: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, Cancer Research Institute, Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan, China.
authors: Yanhui
authors: Y
authors: Bian
authors: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, Cancer Research Institute, Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan, China.
authors: Wei
authors: W
authors: Dang
authors: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, Cancer Research Institute, Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan, China.
authors: Jing
authors: J
authors: Huang
authors: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, Cancer Research Institute, Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan, China.
authors: Ming
authors: M
authors: Zhou
authors: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, Cancer Research Institute, Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan, China.
authors: Yanhong
authors: Y
authors: Zhou
authors: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, Cancer Research Institute, Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan, China.
authors: Wei
authors: W
authors: Xiong
authors: Department of Laboratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Qun
authors: Q
authors: Yan
authors: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, Cancer Research Institute, Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan, China.
authors: Jian
authors: J
authors: Ma
authors: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, Cancer Research Institute, Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan, China.
authors: Guiyuan
authors: G
authors: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D001397:Azoxymethane / Q000633:toxicity; D049109:Cell Proliferation; D003092:Colitis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D015536:Down-Regulation; D055786:Gene Knockout Techniques; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D007781:Lactoferrin / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C490098:LTF protein, human; C552902:Ltf protein, mouse; D016328:NF-kappa B; D016264:Dextran Sulfate; D007781:Lactoferrin; D001397:Azoxymethane