title: Lipopolysaccharide promotes tumorigenicity of hepatic progenitor cells by promoting proliferation and blocking normal differentiation.
abstract: Hepatic progenitor cells (HPCs) are bipotential stem cells that can differentiate into mature hepatocytes or biliary epithelial cells (BECs). They are thought to be involved in repair of liver injury and the incidence of hepatic carcinoma. Their physiology is closely associated with the microenvironment where they reside. Lipopolysaccharide (LPS), an important component of the hepatic pathological microenvironment, is stored in the liver and affects many types of cells in various hepatosis. HPCs may also be influenced by LPS. In this paper, mouse ED13.5 E-cadherin+foetal liver cells were isolated as mouse hepatic progenitor cells (mHPCs). Proliferation of mHPCs was promoted under LPS conditions both in vivo and in vitro. Moreover, LPS enhanced colony formation ability of mHPCs, and blocked them differentiation into mature hepatocytes and formation of a bile duct-liked structure. More importantly, long-term treatment with LPS promoted tumorigenesis of mHPCs in nude mice. Thus, we conclude that LPS may promote aberrant proliferation of mHPCs and restrict their normal differentiation. Long-term exposure of mHPCs to LPS increased the risk of tumour formation. These data provide insight into the links between LPS, HPCs fate, and tumorigenesis, and present novel insight into the relationship between HPCs and their microenvironment.
authors.affiliation: Soochow University, Suzhou, China; Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Li
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Qiu-Dong
authors.initials: QD
authors.lastname: Zhao
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: Han
authors.affiliation: Soochow University, Suzhou, China; Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liang
authors.affiliation: Soochow University, Suzhou, China; Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Pan
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Jing-Ni
authors.initials: JN
authors.lastname: Zhu
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China. Electronic address: 13817669673@163.com.
authors.forename: Meng-Chao
authors.initials: MC
authors.lastname: Wu
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China. Electronic address: weilixin_smmu@163.com.
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Wei
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005865:Gestational Age; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010641:Phenotype; D011725:Pyridines / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects; D055153:Stem Cell Niche; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D059016:Tumor Microenvironment
chemical_list: C530773:3,5-diethoxycarbonyl-1,4-dihydrocollidine; D015820:Cadherins; D008070:Lipopolysaccharides; D011725:Pyridines
keywords: Differentiation; HPCs; Lipopolysaccharide; Proliferation