Inflammation increases NOTCH1 activity via MMP9 and is counteracted by Eicosapentaenoic Acid-free fatty acid in colon cancer cells
Fazio C, Piazzi G, Vitaglione P, Fogliano V, Munarini A, Prossomariti A, Milazzo M, D'Angelo L, Napolitano M, Chieco P, Belluzzi A, Bazzoli F, Ricciardiello L
Scientific reports · 42 citas
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Publicación
- Publicado
- 2016-02-11 · Sci Rep · vol. 6 · número 1 · pág. 20670
- Editorial
- Nature Portfolio
- Citado
- 52 citas · más que el 89% de estudios similares · 2.7× el promedio de su campo
- Referencias
- 53 trabajos
- Acceso
- Acceso abierto (revista) · CC-BY
- Áreas de investigación
- Cancer, Hypoxia, and Metabolism · Cancer, Lipids, and Metabolism · Cancer-related molecular mechanisms research
- Palabras clave
- Eicosapentaenoic acid, Inflammation, MMP9, Cancer research, Colorectal cancer, Chemistry, Polyunsaturated fatty acid, Downregulation and upregulation, Cancer, Fatty acid, Biology, Medicine, Immunology, Biochemistry, Internal medicine
- MeSH
- monocytes, cell line, hct116 cells, ht29 cells, humans, inflammation, tetradecanoylphorbol acetate, lipopolysaccharides, eicosapentaenoic acid, cytokines, culture media, conditioned, signal transduction, cell differentiation, cell movement, gene expression regulation, receptor, notch1, matrix metalloproteinase 9, epithelial-mesenchymal transition
13 autores
- Chiara Di Fazio🇮🇹IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola; University of Bologna
- Giulia Piazzi🇮🇹IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola; University of Bologna
- Paola Vitaglione🇮🇹University of Naples Federico II
- Vincenzo Fogliano🇳🇱Wageningen University & Research
- Alessandra Munarini🇮🇹IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola; University of Bologna
- Anna Prossomariti🇮🇹IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola; University of Bologna
- Maddalena Milazzo🇮🇹IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola; University of Bologna
- Leonarda D’Angelo🇮🇹IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola; University of Bologna
- Manuela Napolitano🇮🇹IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola; University of Bologna
- Pasquale Chieco🇮🇹IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola; University of Bologna
- Andrea Belluzzi🇮🇹IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola
- Franco Bazzoli🇮🇹University of Bologna
- Luigi Ricciardiello🇮🇹 · autor de correspondenciaIRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola; University of Bologna
Resumen
El texto original del estudio, en el idioma en que se publicó.
Aberrant NOTCH1 signalling is critically involved in multiple models of colorectal cancer (CRC) and a prominent role of NOTCH1 activity during inflammation has emerged. Epithelial to Mesenchymal Transition (EMT), a crucial event promoting malignant transformation, is regulated by inflammation and Metalloproteinase-9 (MMP9) plays an important role in this process. Eicosapentaenoic Acid (EPA), an omega-3 polyunsaturated fatty acid, was shown to prevent colonic tumors in different settings. We recently found that an extra-pure formulation of EPA as Free Fatty Acid (EPA-FFA) protects from colon cancer development in a mouse model of Colitis-Associated Cancer (CAC) through modulation of NOTCH1 signalling. In this study, we exposed colon cancer cells to an inflammatory stimulus represented by a cytokine-enriched Conditioned Medium (CM), obtained from THP1-differentiated macrophages. We found, for the first time, that CM strongly up-regulated NOTCH1 signalling and EMT markers, leading to increased invasiveness. Importantly, NOTCH1 signalling was dependent on MMP9 activity, upon CM exposure. We show that a non-cytotoxic pre-treatment with EPA-FFA antagonizes the effect of inflammation on NOTCH1 signalling, with reduction of MMP9 activity and invasiveness. In conclusion, our data suggest that, in CRC cells, inflammation induces NOTCH1 activity through MMP9 up-regulation and that this mechanism can be counteracted by EPA-FFA.
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