title: Suppression of mucin 2 promotes interleukin-6 secretion and tumor growth in an orthotopic immune-competent colon cancer animal model.
abstract: Mucin 2 (MUC2) is the major secreted mucin of the large intestine and is expressed by adenomas and mucinous carcinomas. Since colon cancer is associated with a proinflammatory microenvironment and dysregulated MUC2 expression, the aim of this study was to characterize the effects of MUC2 gene expression in colon tumor progression using colonic cancer cells. CT26 colon cancer cells were stably transfected with MUC2 siRNA (MUC2 RNAi) or a control construct containing a nonspecific sequence (scrambled RNAi). Expression of MUC2 was significantly decreased in the MUC2 RNAi cell clones. Although MUC2 suppression did not affect the cell growth of colon cancer cells in vitro, MUC2 knockdown promoted tumor growth in an orthotopic colon cancer model in vivo. MUC2 silencing also increased interleukin (IL)-6 secretion by colon cancer cells. IL-6 neutralization attenuated tumor formation by MUC2 RNAi cells; it also increased CD8 T cell infiltration into the peritoneum. Taken together, to the best of our knowledge, this is the first study indicating that the immune response to cancer cells plays an important role in tumor growth regulated by MUC2. Furthermore, given the effects of MUC2 on IL-6 secretion, its targeting may represent a potentially useful strategy to treat colonic carcinomas.
authors.affiliation: Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C.
authors.forename: Yan-Shen
authors.initials: YS
authors.lastname: Shan
authors.affiliation: Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C.
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Hsu
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C.
authors.forename: Ming-Derg
authors.initials: MD
authors.lastname: Lai
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C.
authors.forename: Meng-Chi
authors.initials: MC
authors.lastname: Yen
authors.affiliation: Laboratory Animal Center, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C.
authors.forename: Jung-Hua
authors.initials: JH
authors.lastname: Fang
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C.
authors.forename: Tzu-Yang
authors.initials: TY
authors.lastname: Weng
authors.affiliation: Department of Senior Citizen Service Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan, R.O.C.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Chen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D055785:Gene Knockdown Techniques; D007121:Immunocompetence; D015850:Interleukin-6 / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D055262:Mucin-2 / Q000235:genetics* / Q000378:metabolism; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000235:genetics; D047368:Tumor Burden
chemical_list: D015850:Interleukin-6; C524626:Muc2 protein, mouse; D055262:Mucin-2; D034741:RNA, Small Interfering