Cargando…

BIOL-09. PROTEOMIC ANALYSES REVEAL THAT CO-CULTURE OF DIFFUSE INTRINSIC PONTINE GLIOME (DIPG) WITH CORTICAL ORGANOIDS ALTERS CELL ADHESION, DNA SYNTHESIS AND REPLICATION, AND DENDRITIC GROWTH SIGNALLING

Diffuse Intrinsic Pontine Gliomas (DIPGs) are deadly brain cancers in children for which there is currently no effective treatment. In part, this can be attributed to preclinical models that lack essential elements of the in vivo tissue environment, resulting in treatments that appear promising prec...

Descripción completa

Detalles Bibliográficos
Autores principales: Prior, Victoria, Maksour, Simon, Miellet, Sara, Hulme, Amy, Mirzaei, Mehdi, Wu, Yunqi, Dottori, Mirella, O’Neill, Geraldine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259937/
http://dx.doi.org/10.1093/neuonc/noad073.028
_version_ 1785057749843836928
author Prior, Victoria
Maksour, Simon
Miellet, Sara
Hulme, Amy
Mirzaei, Mehdi
Wu, Yunqi
Dottori, Mirella
O’Neill, Geraldine
author_facet Prior, Victoria
Maksour, Simon
Miellet, Sara
Hulme, Amy
Mirzaei, Mehdi
Wu, Yunqi
Dottori, Mirella
O’Neill, Geraldine
author_sort Prior, Victoria
collection PubMed
description Diffuse Intrinsic Pontine Gliomas (DIPGs) are deadly brain cancers in children for which there is currently no effective treatment. In part, this can be attributed to preclinical models that lack essential elements of the in vivo tissue environment, resulting in treatments that appear promising preclinically, but fail to result in effective cures. Recently developed co-culture models combining stem cell-derived brain organoids with brain cancer cells provide tissue dimensionality and a human-relevant tissue-like microenvironment. As these models are technically challenging and time consuming it is imperative to establish whether interaction with the organoid influences DIPG biology and thus warrants their use. To address this question, we cultured DIPG cells with GFP-expressing cortical organoids. We created “mosaic” co-cultures enriched for tumour cell-neuronal cell interactions, where disaggregated spheroids and organoids were mixed and allowed to reform, versus “assembloid” co-cultures enriched for tumour cell-tumour cell interactions, where preformed tumour spheroids and organoids were combined. Sequential window acquisition of all theoretical mass spectra (SWATH-MS) was used to analyse the proteomes of DIPG fractions isolated by flow-assisted cell sorting. Control proteomes from DIPG spheroids were compared with DIPG cells isolated from mosaic and assembloid co-cultures. This revealed that tumour cell adhesion was reduced, and DNA synthesis and replication were increased, in DIPG cells under either co-culture condition. By contrast, the mosaic co-culture was alone associated with pathways implicated in dendrite growth. We propose that co-culture with brain organoids is a valuable tool to parse the contribution of the brain microenvironment to DIPG tumour biology.
format Online
Article
Text
id pubmed-10259937
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-102599372023-06-13 BIOL-09. PROTEOMIC ANALYSES REVEAL THAT CO-CULTURE OF DIFFUSE INTRINSIC PONTINE GLIOME (DIPG) WITH CORTICAL ORGANOIDS ALTERS CELL ADHESION, DNA SYNTHESIS AND REPLICATION, AND DENDRITIC GROWTH SIGNALLING Prior, Victoria Maksour, Simon Miellet, Sara Hulme, Amy Mirzaei, Mehdi Wu, Yunqi Dottori, Mirella O’Neill, Geraldine Neuro Oncol Final Category: Basic Biology/Stem Cells/Models - BIOL Diffuse Intrinsic Pontine Gliomas (DIPGs) are deadly brain cancers in children for which there is currently no effective treatment. In part, this can be attributed to preclinical models that lack essential elements of the in vivo tissue environment, resulting in treatments that appear promising preclinically, but fail to result in effective cures. Recently developed co-culture models combining stem cell-derived brain organoids with brain cancer cells provide tissue dimensionality and a human-relevant tissue-like microenvironment. As these models are technically challenging and time consuming it is imperative to establish whether interaction with the organoid influences DIPG biology and thus warrants their use. To address this question, we cultured DIPG cells with GFP-expressing cortical organoids. We created “mosaic” co-cultures enriched for tumour cell-neuronal cell interactions, where disaggregated spheroids and organoids were mixed and allowed to reform, versus “assembloid” co-cultures enriched for tumour cell-tumour cell interactions, where preformed tumour spheroids and organoids were combined. Sequential window acquisition of all theoretical mass spectra (SWATH-MS) was used to analyse the proteomes of DIPG fractions isolated by flow-assisted cell sorting. Control proteomes from DIPG spheroids were compared with DIPG cells isolated from mosaic and assembloid co-cultures. This revealed that tumour cell adhesion was reduced, and DNA synthesis and replication were increased, in DIPG cells under either co-culture condition. By contrast, the mosaic co-culture was alone associated with pathways implicated in dendrite growth. We propose that co-culture with brain organoids is a valuable tool to parse the contribution of the brain microenvironment to DIPG tumour biology. Oxford University Press 2023-06-12 /pmc/articles/PMC10259937/ http://dx.doi.org/10.1093/neuonc/noad073.028 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Final Category: Basic Biology/Stem Cells/Models - BIOL
Prior, Victoria
Maksour, Simon
Miellet, Sara
Hulme, Amy
Mirzaei, Mehdi
Wu, Yunqi
Dottori, Mirella
O’Neill, Geraldine
BIOL-09. PROTEOMIC ANALYSES REVEAL THAT CO-CULTURE OF DIFFUSE INTRINSIC PONTINE GLIOME (DIPG) WITH CORTICAL ORGANOIDS ALTERS CELL ADHESION, DNA SYNTHESIS AND REPLICATION, AND DENDRITIC GROWTH SIGNALLING
title BIOL-09. PROTEOMIC ANALYSES REVEAL THAT CO-CULTURE OF DIFFUSE INTRINSIC PONTINE GLIOME (DIPG) WITH CORTICAL ORGANOIDS ALTERS CELL ADHESION, DNA SYNTHESIS AND REPLICATION, AND DENDRITIC GROWTH SIGNALLING
title_full BIOL-09. PROTEOMIC ANALYSES REVEAL THAT CO-CULTURE OF DIFFUSE INTRINSIC PONTINE GLIOME (DIPG) WITH CORTICAL ORGANOIDS ALTERS CELL ADHESION, DNA SYNTHESIS AND REPLICATION, AND DENDRITIC GROWTH SIGNALLING
title_fullStr BIOL-09. PROTEOMIC ANALYSES REVEAL THAT CO-CULTURE OF DIFFUSE INTRINSIC PONTINE GLIOME (DIPG) WITH CORTICAL ORGANOIDS ALTERS CELL ADHESION, DNA SYNTHESIS AND REPLICATION, AND DENDRITIC GROWTH SIGNALLING
title_full_unstemmed BIOL-09. PROTEOMIC ANALYSES REVEAL THAT CO-CULTURE OF DIFFUSE INTRINSIC PONTINE GLIOME (DIPG) WITH CORTICAL ORGANOIDS ALTERS CELL ADHESION, DNA SYNTHESIS AND REPLICATION, AND DENDRITIC GROWTH SIGNALLING
title_short BIOL-09. PROTEOMIC ANALYSES REVEAL THAT CO-CULTURE OF DIFFUSE INTRINSIC PONTINE GLIOME (DIPG) WITH CORTICAL ORGANOIDS ALTERS CELL ADHESION, DNA SYNTHESIS AND REPLICATION, AND DENDRITIC GROWTH SIGNALLING
title_sort biol-09. proteomic analyses reveal that co-culture of diffuse intrinsic pontine gliome (dipg) with cortical organoids alters cell adhesion, dna synthesis and replication, and dendritic growth signalling
topic Final Category: Basic Biology/Stem Cells/Models - BIOL
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259937/
http://dx.doi.org/10.1093/neuonc/noad073.028
work_keys_str_mv AT priorvictoria biol09proteomicanalysesrevealthatcocultureofdiffuseintrinsicpontinegliomedipgwithcorticalorganoidsalterscelladhesiondnasynthesisandreplicationanddendriticgrowthsignalling
AT maksoursimon biol09proteomicanalysesrevealthatcocultureofdiffuseintrinsicpontinegliomedipgwithcorticalorganoidsalterscelladhesiondnasynthesisandreplicationanddendriticgrowthsignalling
AT mielletsara biol09proteomicanalysesrevealthatcocultureofdiffuseintrinsicpontinegliomedipgwithcorticalorganoidsalterscelladhesiondnasynthesisandreplicationanddendriticgrowthsignalling
AT hulmeamy biol09proteomicanalysesrevealthatcocultureofdiffuseintrinsicpontinegliomedipgwithcorticalorganoidsalterscelladhesiondnasynthesisandreplicationanddendriticgrowthsignalling
AT mirzaeimehdi biol09proteomicanalysesrevealthatcocultureofdiffuseintrinsicpontinegliomedipgwithcorticalorganoidsalterscelladhesiondnasynthesisandreplicationanddendriticgrowthsignalling
AT wuyunqi biol09proteomicanalysesrevealthatcocultureofdiffuseintrinsicpontinegliomedipgwithcorticalorganoidsalterscelladhesiondnasynthesisandreplicationanddendriticgrowthsignalling
AT dottorimirella biol09proteomicanalysesrevealthatcocultureofdiffuseintrinsicpontinegliomedipgwithcorticalorganoidsalterscelladhesiondnasynthesisandreplicationanddendriticgrowthsignalling
AT oneillgeraldine biol09proteomicanalysesrevealthatcocultureofdiffuseintrinsicpontinegliomedipgwithcorticalorganoidsalterscelladhesiondnasynthesisandreplicationanddendriticgrowthsignalling