Lactoferrin deficiency induces a pro-metastatic tumor microenvironment through recruiting myeloid-derived suppressor cells in mice.

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Abstrakt

Tytuł:: Lactoferrin deficiency induces a pro-metastatic tumor microenvironment through recruiting myeloid-derived suppressor cells in mice.
Autorzy:: Wei L; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Third Xiangya Hospital, Central South University, Changsha, China.; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China.; Key Laboratory of Carcinogenesis of Ministry of Health, Changsha, China.; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Changsha, China.; Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Zhang X; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Third Xiangya Hospital, Central South University, Changsha, China.; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China.; Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Wang J; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China.
Ye Q; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China.
Zheng X; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China.
Peng Q; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China.
Zheng Y; Center for Medical Research, Second Xiangya Hospital, Central South University, Changsha, China.
Liu P; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China.
Zhang X; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China.
Li Z; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China.
Liu C; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China.
Yan Q; Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, China.
Li G; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Third Xiangya Hospital, Central South University, Changsha, China.; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China.; Key Laboratory of Carcinogenesis of Ministry of Health, Changsha, China.; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Changsha, China.
Ma J; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Third Xiangya Hospital, Central South University, Changsha, China. .; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China. .; Key Laboratory of Carcinogenesis of Ministry of Health, Changsha, China. .; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Changsha, China. .; Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China. .
Źródło:: Oncogene [Oncogene] 2020 Jan; Vol. 39 (1), pp. 122-135. Date of Electronic Publication: 2019 Aug 28.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: <2002->: Basingstoke : Nature Publishing Group
Original Publication: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987-
MeSH Terms:: Lactoferrin/*genetics
Melanoma, Experimental/*genetics
Myeloid-Derived Suppressor Cells/*metabolism
Toll-Like Receptor 9/*genetics
Animals ; Apoptosis/genetics ; Cell Differentiation/genetics ; Cell Line, Tumor ; Disease Models, Animal ; Gene Expression Regulation, Neoplastic/genetics ; Heterografts ; Humans ; Immunity, Innate/genetics ; Lactoferrin/deficiency ; Lactoferrin/pharmacology ; Lung/metabolism ; Lung/pathology ; Melanoma, Experimental/pathology ; Mice ; Mice, Knockout ; Myeloid-Derived Suppressor Cells/pathology ; Neoplasm Metastasis ; Signal Transduction/genetics ; Toll-Like Receptor 9/agonists ; Tumor Microenvironment/genetics
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Substance Nomenclature:: 0 (Toll-Like Receptor 9)
EC 3.4.21.- (Lactoferrin)
Entry Date(s):: Date Created: 20190830 Date Completed: 20200420 Latest Revision: 20210303
Update Code:: 20240104
DOI:: 10.1038/s41388-019-0970-8
PMID:: 31462711
: Czasopismo naukowe

Lactoferrin, an innate immunity molecule, is involved in anti-inflammatory, anti-microbial, and anti-tumor activities. We previously reported that lactoferrin is downregulated in specimens of nasopharyngeal carcinoma and negatively associated with tumor progression and metastasis of patients with nasopharyngeal carcinoma. However, the relationship between lactoferrin and the pro-metastatic microenvironment has not been reported yet. Here, by using the lactoferrin knockout mouse, we found that lactoferrin deficiency facilitated melanoma cells metastasizing to lungs, through recruiting myeloid-derived suppressor cells (MDSCs) in the lungs. Mechanistic studies showed that in the lung microenvironment of the lactoferrin knockout mice, the TLR9 signaling was the most repressed signaling. Lactoferrin can induce MDSCs differentiation and apoptosis, as well as upregulate TLR9 expression. TLR9 agonist or lactoferrin treatment can rescue this phenotype in the tumor metastasis mouse model. Our results suggest a protective role of lactoferrin in cancer metastasis, along with a deficiency in certain components of the innate immune system, may lead to a pro-metastatic tumor microenvironment.

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