title: Transforming growth factor-beta1 (TGF-beta1) and acetylcholine (ACh) alter nitric oxide (NO) and interleukin-1beta (IL-1beta) secretion in human colon adenocarcinoma cells.
abstract: Colon adenocarcinoma is one of the most common fatal malignancies in Western countries. Progression of this cancer is dependent on tumor microenvironmental signaling molecules such as transforming growth factor-beta (TGF-beta) or acetylcholine (ACh). The present study was conducted to assess the influence of recombinant human transforming growth factor (rhTGF)-beta1 or ACh on nitric oxide (NO) and interleukin-1beta (IL-1beta) secretion by three human colon adenocarcinoma cell lines: HT29, LS180, and SW948, derived from different grade tumors (Duke's stage). The cells were cultured in 2D and 3D (spheroids) conditions. Colon carcinoma cells exhibited different sensitivities to rhTGF-beta1 or ACh dependent on the tumor grade and the culture model. ACh exhibited significant inhibitory effects towards NO, endothelial nitric oxide synthase (eNOS), and IL-1beta secretion especially by tumor cells derived form Duke's C stage of colon carcinoma. rhTGF-beta1 also decreased NO, IL-1beta, and eNOS expression, but its effect was lower than that observed after the administration of ACh. The inhibition of NO and IL-1beta production was more striking in 3D tumor spheroids than in 2D culture monolayers. Taken together, the TGF-beta1-ACh axis may regulate colon carcinoma progression and metastasis by altering NO secretion and influence inflammatory responses by modulating IL-1beta production.
authors: Department of Virology and Immunology, Institute of Microbiology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland. rpaduch@poczta.umcs.lublin.pl
authors: Roman
authors: R
authors: Paduch
authors: Martyna
authors: M
authors: Kandefer-Szerszeń
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D053583:Interleukin-1beta; D053773:Transforming Growth Factor beta1; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine