title: CD147 stimulates hepatoma cells escaping from immune surveillance of T cells by interaction with Cyclophilin A.
abstract: T cells play an important role in tumor immune surveillance. CD147 is a member of immunoglobulin superfamily present on the surface of many tumor cells and mediates malignant cell behaviors. Cyclophilin A (CypA) is an intracellular protein promoting inflammation when released from cells. CypA is a natural ligand for CD147. In this study, CD147 specific short hairpin RNAs (shRNA) were transfected into murine hepatocellular carcinoma Hepa1-6 cells to assess the effects of CD147 on hepatoma cells escaping from immune surveillance of T cells. We found extracellular CypA stimulated cell proliferation through CD147 by activating ERK1/2 signaling pathway. Downregulation of CD147 expression on Hepa1-6 cells significantly suppressed tumor progression in vivo, and decreased cell viability when co-cultured with T cells in vitro. Importantly, knockdown of CD147 on Hepa1-6 cells resulted in significantly increased T cells chemotaxis induced by CypA both in vivo and in vitro. These findings provide novel mechanisms how tumor cells escaping from immune surveillance of T cells. We provide a potential therapy for hepatocellular carcinoma by targeting CD147 or CD147-CypA interactions.
authors.affiliation: Department of Biochemistry, Dalian Medical University, 9 South Lvshun Road Western Section, Dalian 116044, Liaoning, China; Department of Parasitology, Dalian Medical University, 9 South Lvshun Road Western Section, Dalian 116044, Liaoning, China.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Ren
authors.affiliation: Department of Biochemistry, Dalian Medical University, 9 South Lvshun Road Western Section, Dalian 116044, Liaoning, China.
authors.forename: Shu-Jing
authors.initials: SJ
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, Dalian Medical University, 9 South Lvshun Road Western Section, Dalian 116044, Liaoning, China.
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Fan
authors.affiliation: Department of Immunology, Dalian Medical University, 9 South Lvshun Road Western Section, Dalian 116044, Liaoning, China.
authors.forename: Shi-Jie
authors.initials: SJ
authors.lastname: Sun
authors.affiliation: Department of Immunology, Dalian Medical University, 9 South Lvshun Road Western Section, Dalian 116044, Liaoning, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Biochemistry, Dalian Medical University, 9 South Lvshun Road Western Section, Dalian 116044, Liaoning, China.
authors.forename: Arshad Ahmed
authors.initials: AA
authors.lastname: Padhiar
authors.affiliation: Department of Biochemistry, Dalian Medical University, 9 South Lvshun Road Western Section, Dalian 116044, Liaoning, China; School of Life Science and Medicine, Dalian University of Technology, 2 Linggong Road, Dalian 116024, Liaoning, China. Electronic address: jnzhang@dlut.edu.cn.
authors.forename: Jia-Ning
authors.initials: JN
authors.lastname: Zhang
mesh_terms: D000818:Animals; D051926:Basigin / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D018920:Coculture Techniques; D021984:Cyclophilin A / Q000378:metabolism* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D057131:Immune Evasion / Q000187:drug effects; D007157:Immunologic Surveillance; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology; D008810:Mice, Inbred C57BL; D011485:Protein Binding / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; D051926:Basigin; D048049:Extracellular Signal-Regulated MAP Kinases; D021984:Cyclophilin A
keywords: CD147; Chemotaxis; Cyclophilin A; Hepatocellular carcinoma; Tumor immunesurveillance