Monocytes acquire prostate cancer specific chromatin conformations upon indirect co-culture with prostate cancer cells
BackgroundThree-dimensional chromosome loop conformations are powerful regulators of gene expression. These chromosome conformations can be detected both in tumour and in circulating cells and have significant disease biomarker potential. We have recently detected specific chromosome conformations i...
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Frontiers Media S.A.
2022-08-01
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Series: | Frontiers in Oncology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.990842/full |
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author | Heba Alshaker Ewan Hunter Matthew Salter Aroul Ramadass Willem Westra Mathias Winkler Jayne Green Alexandre Akoulitchev Dmitri Pchejetski |
author_facet | Heba Alshaker Ewan Hunter Matthew Salter Aroul Ramadass Willem Westra Mathias Winkler Jayne Green Alexandre Akoulitchev Dmitri Pchejetski |
author_sort | Heba Alshaker |
collection | DOAJ |
description | BackgroundThree-dimensional chromosome loop conformations are powerful regulators of gene expression. These chromosome conformations can be detected both in tumour and in circulating cells and have significant disease biomarker potential. We have recently detected specific chromosome conformations in circulating cells of patients with prostate cancer (PCa) which were similar to ones found in their primary tumours, however, the possibility of horizontal transfer of chromosome conformations was not studied previously.MethodsHuman monocytes (U937) were co-cultured in Boyden chambers through 0.4 uM membrane with or without PC-3 human PCa cells or their conditioned media and a custom DNA microarray for 900,000 chromosomal loops covering all coding loci and non-coding RNA genes was performed on each part of the co-culture system.ResultsWe have detected 684 PC-3 cell-specific chromosome conformations across the whole genome that were absent in naïve monocytes but appeared in monocytes co-cultured with PC-3 cells or with PC-3-conditioned media. Comparing PC3-specific conformations to the ones we have previously detected in systemic circulation of high-risk PCa patients revealed 9 positive loops present in both settings.ConclusionsOur results demonstrate for the first time a proof of concept for horizontal transfer of chromosome conformations without direct cell-cell contact. This carries high clinical relevance as we have previously observed chromatin conformations in circulating cells of patients with melanoma and PCa similar to ones in their primary tumours. These changes can be used as highly specific biomarkers for diagnosis and prognosis. Further studies are required to elucidate the specific mechanism of chromosome conformations transfer and its clinical significance in particular diseases. |
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id | doaj.art-7a4c9e4f4d964364a0dae4675552a82c |
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issn | 2234-943X |
language | English |
last_indexed | 2024-04-13T18:32:19Z |
publishDate | 2022-08-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Oncology |
spelling | doaj.art-7a4c9e4f4d964364a0dae4675552a82c2022-12-22T02:35:02ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-08-011210.3389/fonc.2022.990842990842Monocytes acquire prostate cancer specific chromatin conformations upon indirect co-culture with prostate cancer cellsHeba Alshaker0Ewan Hunter1Matthew Salter2Aroul Ramadass3Willem Westra4Mathias Winkler5Jayne Green6Alexandre Akoulitchev7Dmitri Pchejetski8School of Medicine, University of East Anglia, Norwich, United KingdomOxford BioDynamics Limited, Oxford, United KingdomOxford BioDynamics Limited, Oxford, United KingdomOxford BioDynamics Limited, Oxford, United KingdomOxford BioDynamics Limited, Oxford, United KingdomDepartment of Surgery and Cancer, Imperial College London, London, United KingdomOxford BioDynamics Limited, Oxford, United KingdomOxford BioDynamics Limited, Oxford, United KingdomSchool of Medicine, University of East Anglia, Norwich, United KingdomBackgroundThree-dimensional chromosome loop conformations are powerful regulators of gene expression. These chromosome conformations can be detected both in tumour and in circulating cells and have significant disease biomarker potential. We have recently detected specific chromosome conformations in circulating cells of patients with prostate cancer (PCa) which were similar to ones found in their primary tumours, however, the possibility of horizontal transfer of chromosome conformations was not studied previously.MethodsHuman monocytes (U937) were co-cultured in Boyden chambers through 0.4 uM membrane with or without PC-3 human PCa cells or their conditioned media and a custom DNA microarray for 900,000 chromosomal loops covering all coding loci and non-coding RNA genes was performed on each part of the co-culture system.ResultsWe have detected 684 PC-3 cell-specific chromosome conformations across the whole genome that were absent in naïve monocytes but appeared in monocytes co-cultured with PC-3 cells or with PC-3-conditioned media. Comparing PC3-specific conformations to the ones we have previously detected in systemic circulation of high-risk PCa patients revealed 9 positive loops present in both settings.ConclusionsOur results demonstrate for the first time a proof of concept for horizontal transfer of chromosome conformations without direct cell-cell contact. This carries high clinical relevance as we have previously observed chromatin conformations in circulating cells of patients with melanoma and PCa similar to ones in their primary tumours. These changes can be used as highly specific biomarkers for diagnosis and prognosis. Further studies are required to elucidate the specific mechanism of chromosome conformations transfer and its clinical significance in particular diseases.https://www.frontiersin.org/articles/10.3389/fonc.2022.990842/fullprostate cancernucleome3Cblood testhorizontal gene transfer |
spellingShingle | Heba Alshaker Ewan Hunter Matthew Salter Aroul Ramadass Willem Westra Mathias Winkler Jayne Green Alexandre Akoulitchev Dmitri Pchejetski Monocytes acquire prostate cancer specific chromatin conformations upon indirect co-culture with prostate cancer cells Frontiers in Oncology prostate cancer nucleome 3C blood test horizontal gene transfer |
title | Monocytes acquire prostate cancer specific chromatin conformations upon indirect co-culture with prostate cancer cells |
title_full | Monocytes acquire prostate cancer specific chromatin conformations upon indirect co-culture with prostate cancer cells |
title_fullStr | Monocytes acquire prostate cancer specific chromatin conformations upon indirect co-culture with prostate cancer cells |
title_full_unstemmed | Monocytes acquire prostate cancer specific chromatin conformations upon indirect co-culture with prostate cancer cells |
title_short | Monocytes acquire prostate cancer specific chromatin conformations upon indirect co-culture with prostate cancer cells |
title_sort | monocytes acquire prostate cancer specific chromatin conformations upon indirect co culture with prostate cancer cells |
topic | prostate cancer nucleome 3C blood test horizontal gene transfer |
url | https://www.frontiersin.org/articles/10.3389/fonc.2022.990842/full |
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