title: MUC5AC protects pancreatic cancer cells from TRAIL-induced death pathways.
abstract: We have previously reported that a specific siRNA transfected MUC5AC could knockdown MUC5AC expression and suppress in vivo tumor growth and metastasis, although it had no effects on in vitro cell growth, cell survival, proliferation and morphology. In the present study, we investigated which host immune cells induced these effects and how the effects were induced using immunocyte-depleted animal models. The tumor growth of SW1990/si-MUC5AC cells, which show no tumor growth when implanted subcutaneously into a nude mouse, was recovered when neutrophils were removed by anti-Gr-1 mAb administration. This result suggests that MUC5AC may suppress the antitumor effects of neutrophils by allowing tumor cells to escape the host immune system. Subsequently, we investigated the effects of MUC5AC on apoptosis induction mediated by TNF-related apoptosis-inducing ligand (TRAIL), one of the antitumor mechanisms of neutrophils. SW1990/si-MUC5AC cells showed significantly increased active caspase 3 expression after the addition of TRAIL. On the other hand, SW1990/si-mock cells showed no such changes. Our results indicate that MUC5AC inhibits TRAIL‑induced apoptosis in human pancreatic cancer and may serve as an important indicator in diagnosis and prognosis.
authors.affiliation: Biomedical Research Laboratories, Kureha Corporation, Shinjuku-ku,                     Tokyo 169-8503, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Hoshi
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Sawada
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Uchida
authors.forename: Hiroko
authors.initials: H
authors.lastname: Iijima
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kimura
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Wanibuchi
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009504:Neutrophils / Q000276:immunology; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D016209:Interleukin-8; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D034741:RNA, Small Interfering; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; D053148:Caspase 3