Details

Autor(en) / Beteiligte

• Rossin, D.
• Dias, I.H.K.
• Solej, M.
• Milic, I.
• Pitt, A.R.
• Iaia, N.
• Scoppapietra, L.
• Devitt, A.
• Nano, M.
• Degiuli, M.
• Volante, M.
• Caccia, C.
• Leoni, V.
• Griffiths, H.R.
• Spickett, C.M.
• Poli, G.
• Biasi, F.

Titel

Increased production of 27-hydroxycholesterol in human colorectal cancer advanced stage: Possible contribution to cancer cell survival and infiltration

Ist Teil von

• Free radical biology & medicine, 2019-05, Vol.136, p.35-44

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. [Display omitted] •27-hydroxycholesterol (27HC) is involved in colorectal cancer (CRC) progression.•27HC reaches high pathological concentrations in CRC advanced stage in humans.•27HC in vitro increases cell release of pro-tumor inflammatory mediators.•27HC favors survival and invasiveness-related cell signals in intestinal cells.