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Transcriptome of GH-producing pituitary neuroendocrine tumours and models are significantly affected by somatostatin analogues

Pituitary neuroendocrine tumours (PitNETs) are neoplasms of the pituitary that overproduce hormones or cause unspecific symptoms due to mass effect. Growth hormone overproducing GH-producing PitNETs cause acromegaly leading to connective tissue, metabolic or oncologic disorders. The medical treatmen...

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Autores principales: Saksis, Rihards, Rogoza, Olesja, Niedra, Helvijs, Megnis, Kaspars, Mandrika, Ilona, Balcere, Inga, Steina, Liva, Stukens, Janis, Breiksa, Austra, Nazarovs, Jurijs, Sokolovska, Jelizaveta, Konrade, Ilze, Peculis, Raitis, Rovite, Vita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9922463/
https://www.ncbi.nlm.nih.gov/pubmed/36774501
http://dx.doi.org/10.1186/s12935-023-02863-4
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author Saksis, Rihards
Rogoza, Olesja
Niedra, Helvijs
Megnis, Kaspars
Mandrika, Ilona
Balcere, Inga
Steina, Liva
Stukens, Janis
Breiksa, Austra
Nazarovs, Jurijs
Sokolovska, Jelizaveta
Konrade, Ilze
Peculis, Raitis
Rovite, Vita
author_facet Saksis, Rihards
Rogoza, Olesja
Niedra, Helvijs
Megnis, Kaspars
Mandrika, Ilona
Balcere, Inga
Steina, Liva
Stukens, Janis
Breiksa, Austra
Nazarovs, Jurijs
Sokolovska, Jelizaveta
Konrade, Ilze
Peculis, Raitis
Rovite, Vita
author_sort Saksis, Rihards
collection PubMed
description Pituitary neuroendocrine tumours (PitNETs) are neoplasms of the pituitary that overproduce hormones or cause unspecific symptoms due to mass effect. Growth hormone overproducing GH-producing PitNETs cause acromegaly leading to connective tissue, metabolic or oncologic disorders. The medical treatment of acromegaly is somatostatin analogues (SSA) in specific cases combined with dopamine agonists (DA), but almost half of patients display partial or full SSA resistance and potential causes of this are unknown. In this study we investigated transcriptomic landscape of GH-producing PitNETs on several levels and functional models—tumour tissue of patients with and without SSA preoperative treatment, tumour derived pituispheres and GH3 cell line incubated with SSA to study effect of medication on gene expression. MGI sequencing platform was used to sequence total RNA from PitNET tissue, pituispheres, mesenchymal stromal stem-like cells (MSC), and GH3 cell cultures, and data were analysed with Salmon—DeSeq2 pipeline. We observed that the GH-producing PitNETs have distinct changes in growth hormone related pathways related to its functional status alongside inner cell signalling, ion transport, cell adhesion and extracellular matrix characteristic patterns. In pituispheres model, treatment regimens (octreotide and cabergoline) affect specific cell proliferation (MKI67) and core functionality pathways (RYR2, COL8A2, HLA-G, ARFGAP1, TGFBR2). In GH3 cells we observed that medication did not have transcriptomic effects similar to preoperative treatment in PitNET tissue or pituisphere model. This study highlights the importance of correct model system selection for cell transcriptomic profiling and data interpretation that could be achieved in future by incorporating NGS methods and detailed cell omics profiling in PitNET model research. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-023-02863-4.
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spelling pubmed-99224632023-02-13 Transcriptome of GH-producing pituitary neuroendocrine tumours and models are significantly affected by somatostatin analogues Saksis, Rihards Rogoza, Olesja Niedra, Helvijs Megnis, Kaspars Mandrika, Ilona Balcere, Inga Steina, Liva Stukens, Janis Breiksa, Austra Nazarovs, Jurijs Sokolovska, Jelizaveta Konrade, Ilze Peculis, Raitis Rovite, Vita Cancer Cell Int Research Pituitary neuroendocrine tumours (PitNETs) are neoplasms of the pituitary that overproduce hormones or cause unspecific symptoms due to mass effect. Growth hormone overproducing GH-producing PitNETs cause acromegaly leading to connective tissue, metabolic or oncologic disorders. The medical treatment of acromegaly is somatostatin analogues (SSA) in specific cases combined with dopamine agonists (DA), but almost half of patients display partial or full SSA resistance and potential causes of this are unknown. In this study we investigated transcriptomic landscape of GH-producing PitNETs on several levels and functional models—tumour tissue of patients with and without SSA preoperative treatment, tumour derived pituispheres and GH3 cell line incubated with SSA to study effect of medication on gene expression. MGI sequencing platform was used to sequence total RNA from PitNET tissue, pituispheres, mesenchymal stromal stem-like cells (MSC), and GH3 cell cultures, and data were analysed with Salmon—DeSeq2 pipeline. We observed that the GH-producing PitNETs have distinct changes in growth hormone related pathways related to its functional status alongside inner cell signalling, ion transport, cell adhesion and extracellular matrix characteristic patterns. In pituispheres model, treatment regimens (octreotide and cabergoline) affect specific cell proliferation (MKI67) and core functionality pathways (RYR2, COL8A2, HLA-G, ARFGAP1, TGFBR2). In GH3 cells we observed that medication did not have transcriptomic effects similar to preoperative treatment in PitNET tissue or pituisphere model. This study highlights the importance of correct model system selection for cell transcriptomic profiling and data interpretation that could be achieved in future by incorporating NGS methods and detailed cell omics profiling in PitNET model research. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-023-02863-4. BioMed Central 2023-02-11 /pmc/articles/PMC9922463/ /pubmed/36774501 http://dx.doi.org/10.1186/s12935-023-02863-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Saksis, Rihards
Rogoza, Olesja
Niedra, Helvijs
Megnis, Kaspars
Mandrika, Ilona
Balcere, Inga
Steina, Liva
Stukens, Janis
Breiksa, Austra
Nazarovs, Jurijs
Sokolovska, Jelizaveta
Konrade, Ilze
Peculis, Raitis
Rovite, Vita
Transcriptome of GH-producing pituitary neuroendocrine tumours and models are significantly affected by somatostatin analogues
title Transcriptome of GH-producing pituitary neuroendocrine tumours and models are significantly affected by somatostatin analogues
title_full Transcriptome of GH-producing pituitary neuroendocrine tumours and models are significantly affected by somatostatin analogues
title_fullStr Transcriptome of GH-producing pituitary neuroendocrine tumours and models are significantly affected by somatostatin analogues
title_full_unstemmed Transcriptome of GH-producing pituitary neuroendocrine tumours and models are significantly affected by somatostatin analogues
title_short Transcriptome of GH-producing pituitary neuroendocrine tumours and models are significantly affected by somatostatin analogues
title_sort transcriptome of gh-producing pituitary neuroendocrine tumours and models are significantly affected by somatostatin analogues
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9922463/
https://www.ncbi.nlm.nih.gov/pubmed/36774501
http://dx.doi.org/10.1186/s12935-023-02863-4
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