title: Chemokine (C-C Motif) Ligand 5 is Involved in Tumor-Associated Dendritic Cell-Mediated Colon Cancer Progression Through Non-Coding RNA MALAT-1.
abstract: Tumor micro-environment is a critical factor in the development of cancer. The aim of this study was to investigate the inflammatory cytokines secreted by tumor-associated dendritic cells (TADCs) that contribute to enhanced migration, invasion, and epithelial-to-mesenchymal transition (EMT) in colon cancer. The administration of recombinant human chemokine (C-C motif) ligand 5 (CCL5), which is largely expressed by colon cancer surrounding TADCs, mimicked the stimulation of TADC-conditioned medium on migration, invasion, and EMT in colon cancer cells. Blocking CCL5 by neutralizing antibodies or siRNA transfection diminished the promotion of cancer progression by TADCs. Tumor-infiltrating CD11c(+) DCs in human colon cancer specimens were shown to produce CCL5. The stimulation of colon cancer progression by TADC-derived CCL5 was associated with the up-regulation of non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), which subsequently increased the expression of Snail. Blocking MALAT-1 significantly decreased the TADC-conditioned medium and CCL5-mediated migration and invasion by decreasing the enhancement of Snail, suggesting that the MALAT-1/Snail pathway plays a critical role in TADC-mediated cancer progression. In conclusion, the inhibition of CCL5 or CCL5-related signaling may be an attractive therapeutic target in colon cancer patients.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Gastrointestinal and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Jung-Yu
authors.initials: JY
authors.lastname: Kan
authors.forename: Deng-Chyang
authors.initials: DC
authors.lastname: Wu
authors.forename: Fang-Jung
authors.initials: FJ
authors.lastname: Yu
authors.forename: Cheng-Ying
authors.initials: CY
authors.lastname: Wu
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Ho
authors.forename: Yen-Jung
authors.initials: YJ
authors.lastname: Chiu
authors.forename: Shu-Fang
authors.initials: SF
authors.lastname: Jian
authors.forename: Jen-Yu
authors.initials: JY
authors.lastname: Hung
authors.forename: Jaw-Yuan
authors.initials: JY
authors.lastname: Wang
authors.forename: Po-Lin
authors.initials: PL
authors.lastname: Kuo
mesh_terms: D002465:Cell Movement; D018946:Chemokine CCL5 / Q000276:immunology / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D062085:RNA, Long Noncoding / Q000378:metabolism*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: C483024:CCL5 protein, human; D018946:Chemokine CCL5; C557041:MALAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering