title: Lung tumor-associated dendritic cell-derived resistin promoted cancer progression by increasing Wolf-Hirschhorn syndrome candidate 1/Twist pathway.
abstract: The interaction between tumors and their microenvironments leads to a vicious cycle, which strengthens both immune suppression and cancer progression. The present study demonstrates for the first time that tumor-associated dendritic cells (TADCs) are a source of resistin, which is responsible for increasing lung cancer epithelial-to-mesenchymal transition. In addition, large amounts of resistin in the condition medium (CM) of TADCs increase cell migration and invasion, as well as the osteolytic bone metastatic properties of lung cancer cells. Neutralization of resistin from TADC-CM prevents the advanced malignancy-inducing features of TADC-CM. Significantly elevated levels of resistin have been observed in mice transplanted with lung cancer cells, tumor-infiltrating CD11c(+) DCs in human lung cancer samples and lung cancer patients' sera. Induction of lung cancer progression by TADC-derived resistin is associated with increased expression of Wolf-Hirschhorn syndrome candidate 1 (WHSC1), a histone methyltransferase. Resistin-induced WHSC1 increases the dimethylation of histone 3 at lysine 36 and decreases the trimethylation of histone 3 at lysine 27 on the promoter of Twist, resulting in an enhancement of the expression of Twist. Knockdown of WHSC1 by small interfering RNA transfection significantly decreases resistin-mediated cancer progression by decreasing the upregulation of Twist, suggesting that WHSC1 plays a critical role in the regulation of Twist by epigenetic modification. Furthermore, mice that received antiresistin antibodies showed a decreased incidence of cancer development and metastasis. These findings suggest that TADC-derived resistin may be a novel candidate in promoting the development of lung cancer.
authors: The Affiliated Senior High School of National Kaohsiung Normal University, Kaohsiung 802, Taiwan.
authors: Chih-Hsin
authors: CH
authors: Kuo
authors: Kuei-Fang
authors: KF
authors: Chen
authors: Shah-Hwa
authors: SH
authors: Chou
authors: Ya-Fang
authors: YF
authors: Huang
authors: Cheng-Ying
authors: CY
authors: Wu
authors: Da-En
authors: DE
authors: Cheng
authors: Yu-Wen
authors: YW
authors: Chen
authors: Chih-Jen
authors: CJ
authors: Yang
authors: Jen-Yu
authors: JY
authors: Hung
authors: Ming-Shyan
authors: MS
authors: Huang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051879:Twist-Related Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D051879:Twist-Related Protein 1; D011495:Histone-Lysine N-Methyltransferase; C419586:NSD2 protein, human