Transforming growth factor-beta1 (TGF-beta1) and acetylcholine (ACh) alter nitric oxide (NO) and interleukin-1beta (IL-1beta) secretion in human colon adenocarcinoma cells.
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.
Paduch
Roman
R
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
Kandefer-Szerszeń
Martyna
M
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*
D053583:Interleukin-1beta; D053773:Transforming Growth Factor beta1; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine