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

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

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)35-44
Number of pages10
JournalFree Radical Biology and Medicine
Volume136
Early online date23 Mar 2019
DOIs
Publication statusPublished - 20 May 2019

Fingerprint

Infiltration
Colorectal Neoplasms
Cell Survival
Cells
Tumors
Neoplasms
Chemokine CCL2
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Interleukin-8
Vascular Endothelial Growth Factor A
Interleukin-6
Modulation
Tissue
Molecules
27-hydroxycholesterol
Up-Regulation
Cell Line
Growth
Oxysterols

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].

Keywords

  • 27-Hydroxycholesterol
  • Akt
  • Colorectal cancer
  • Inflammation
  • MMP
  • Oxysterols
  • Survival signaling

Cite this

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. / Increased production of 27-hydroxycholesterol in human colorectal cancer advanced stage: Possible contribution to cancer cell survival and infiltration. In: Free Radical Biology and Medicine. 2019 ; Vol. 136. pp. 35-44.
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Increased production of 27-hydroxycholesterol in human colorectal cancer advanced stage: Possible contribution to cancer cell survival and infiltration. / 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.

In: Free Radical Biology and Medicine, Vol. 136, 20.05.2019, p. 35-44.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Increased production of 27-hydroxycholesterol in human colorectal cancer advanced stage: Possible contribution to cancer cell survival and infiltration

AU - Rossin, D.

AU - Dias, I.h.k.

AU - Solej, M.

AU - Milic, I.

AU - Pitt, A.r.

AU - Iaia, N.

AU - Scoppapietra, L.

AU - Devitt, A.

AU - Nano, M.

AU - Degiuli, M.

AU - Volante, M.

AU - Caccia, C.

AU - Leoni, V.

AU - Griffiths, H.r.

AU - Spickett, C.m.

AU - Poli, G.

AU - Biasi, F.

N1 - © 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].

PY - 2019/5/20

Y1 - 2019/5/20

N2 - 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.

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KW - Survival signaling

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