1. Increased production of 27-hydroxycholesterol in human colorectal cancer advanced stage: Possible contribution to cancer cell survival and infiltration
- Author
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Fiorella Biasi, Helen R. Griffiths, G. Poli, Mario Nano, Andrew Devitt, Noemi Iaia, Claudio Caccia, Mario Solej, Andrew R. Pitt, Ivana Milic, M. Volante, L. Scoppapietra, M. Degiuli, Corinne M. Spickett, Daniela Rossin, Irundika H.K. Dias, Valerio Leoni, Rossin, D, Dias, I, Solej, M, Milic, I, Pitt, A, Iaia, N, Scoppapietra, L, Devitt, A, Nano, M, Degiuli, M, Volante, M, Caccia, C, Leoni, V, Griffiths, H, Spickett, C, Poli, G, and Biasi, F
- Subjects
0301 basic medicine ,Oxysterol ,Cell Survival ,Colorectal cancer ,Inflammation ,Biochemistry ,Survival signaling ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Physiology (medical) ,medicine ,Humans ,Neoplasm Invasiveness ,Protein kinase B ,27-Hydroxycholesterol ,MMP ,Monocyte ,Akt ,Oxysterols ,medicine.disease ,Hydroxycholesterols ,Vascular endothelial growth factor ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Cancer cell ,Disease Progression ,Cancer research ,Caco-2 Cells ,medicine.symptom ,Colorectal Neoplasms ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
So far, the investigation in cancer cell lines of the modulation of cancer growth and progression by oxysterols, in particular 27-hydroxycholesterol (27HC), has yielded controversial results. The primary aim of this study was the quantitative evaluation of possible changes in 27HC levels during the different steps of colorectal cancer (CRC) progression in humans. A consistent increase in this oxysterol in CRC mass compared to the tumor-adjacent tissue was indeed observed, but only in advanced stages of progression (TNM stage III), a phase in which cancer has spread to nearby sites. To investigate possible pro-tumor properties of 27HC, its effects were studied in vitro in differentiated CaCo-2 cells. Relatively high concentrations of this oxysterol markedly increased the release of pro-inflammatory interleukins 6 and 8, monocyte chemoattractant protein-1, vascular endothelial growth factor, as well as matrix metalloproteinases 2 and 9. The up-regulation of all these molecules, which are potentially able to favor cancer progression, appeared to be dependent upon a net stimulation of Akt signaling exerted by supra-physiological amounts of 27HC.
- Published
- 2019