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...

Full description

Bibliographic Details
Main Authors: Heba Alshaker, Ewan Hunter, Matthew Salter, Aroul Ramadass, Willem Westra, Mathias Winkler, Jayne Green, Alexandre Akoulitchev, Dmitri Pchejetski
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-08-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.990842/full
_version_ 1811339769985105920
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.
first_indexed 2024-04-13T18:32:19Z
format Article
id doaj.art-7a4c9e4f4d964364a0dae4675552a82c
institution Directory Open Access Journal
issn 2234-943X
language English
last_indexed 2024-04-13T18:32:19Z
publishDate 2022-08-01
publisher Frontiers Media S.A.
record_format Article
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
work_keys_str_mv AT hebaalshaker monocytesacquireprostatecancerspecificchromatinconformationsuponindirectcoculturewithprostatecancercells
AT ewanhunter monocytesacquireprostatecancerspecificchromatinconformationsuponindirectcoculturewithprostatecancercells
AT matthewsalter monocytesacquireprostatecancerspecificchromatinconformationsuponindirectcoculturewithprostatecancercells
AT aroulramadass monocytesacquireprostatecancerspecificchromatinconformationsuponindirectcoculturewithprostatecancercells
AT willemwestra monocytesacquireprostatecancerspecificchromatinconformationsuponindirectcoculturewithprostatecancercells
AT mathiaswinkler monocytesacquireprostatecancerspecificchromatinconformationsuponindirectcoculturewithprostatecancercells
AT jaynegreen monocytesacquireprostatecancerspecificchromatinconformationsuponindirectcoculturewithprostatecancercells
AT alexandreakoulitchev monocytesacquireprostatecancerspecificchromatinconformationsuponindirectcoculturewithprostatecancercells
AT dmitripchejetski monocytesacquireprostatecancerspecificchromatinconformationsuponindirectcoculturewithprostatecancercells