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.
|Number of pages||10|
|Journal||Free Radical Biology and Medicine|
|Early online date||23 Mar 2019|
|Publication status||Published - 20 May 2019|
Bibliographical note© 2019, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Funding: Biotechnology and Biological Sciences Research Council [grant number BB/M006298/1]. University of Turin, Italy [grant numbers POLG_RILO_16_01, 2016; BIAF_RILO_17_01], the European Union's Horizon 2020 research and innovation program under the Marie Sklowdowska-Curie [grant agreement number 675132].
- Colorectal cancer
- Survival signaling
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. (2019). Increased production of 27-hydroxycholesterol in human colorectal cancer advanced stage: Possible contribution to cancer cell survival and infiltration. Free Radical Biology and Medicine, 136, 35-44. https://doi.org/10.1016/j.freeradbiomed.2019.03.020