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ALDOC- and ENO2- driven glucose metabolism sustains 3D tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis
BACKGROUND: Metastases are the major cause of cancer-related morbidity and mortality. By the time cancer cells detach from their primary site to eventually spread to distant sites, they need to acquire the ability to survive in non-adherent conditions and to proliferate within a new microenvironment...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10031988/ https://www.ncbi.nlm.nih.gov/pubmed/36945054 http://dx.doi.org/10.1186/s13046-023-02641-0 |
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author | De Vitis, Claudia Battaglia, Anna Martina Pallocca, Matteo Santamaria, Gianluca Mimmi, Maria Chiara Sacco, Alessandro De Nicola, Francesca Gaspari, Marco Salvati, Valentina Ascenzi, Francesca Bruschini, Sara Esposito, Antonella Ricci, Giulia Sperandio, Eleonora Massacci, Alice Prestagiacomo, Licia Elvira Vecchione, Andrea Ricci, Alberto Sciacchitano, Salvatore Salerno, Gerardo French, Deborah Aversa, Ilenia Cereda, Cristina Fanciulli, Maurizio Chiaradonna, Ferdinando Solito, Egle Cuda, Giovanni Costanzo, Francesco Ciliberto, Gennaro Mancini, Rita Biamonte, Flavia |
author_facet | De Vitis, Claudia Battaglia, Anna Martina Pallocca, Matteo Santamaria, Gianluca Mimmi, Maria Chiara Sacco, Alessandro De Nicola, Francesca Gaspari, Marco Salvati, Valentina Ascenzi, Francesca Bruschini, Sara Esposito, Antonella Ricci, Giulia Sperandio, Eleonora Massacci, Alice Prestagiacomo, Licia Elvira Vecchione, Andrea Ricci, Alberto Sciacchitano, Salvatore Salerno, Gerardo French, Deborah Aversa, Ilenia Cereda, Cristina Fanciulli, Maurizio Chiaradonna, Ferdinando Solito, Egle Cuda, Giovanni Costanzo, Francesco Ciliberto, Gennaro Mancini, Rita Biamonte, Flavia |
author_sort | De Vitis, Claudia |
collection | PubMed |
description | BACKGROUND: Metastases are the major cause of cancer-related morbidity and mortality. By the time cancer cells detach from their primary site to eventually spread to distant sites, they need to acquire the ability to survive in non-adherent conditions and to proliferate within a new microenvironment in spite of stressing conditions that may severely constrain the metastatic process. In this study, we gained insight into the molecular mechanisms allowing cancer cells to survive and proliferate in an anchorage-independent manner, regardless of both tumor-intrinsic variables and nutrient culture conditions. METHODS: 3D spheroids derived from lung adenocarcinoma (LUAD) and breast cancer cells were cultured in either nutrient-rich or -restricted culture conditions. A multi-omics approach, including transcriptomics, proteomics, and metabolomics, was used to explore the molecular changes underlying the transition from 2 to 3D cultures. Small interfering RNA-mediated loss of function assays were used to validate the role of the identified differentially expressed genes and proteins in H460 and HCC827 LUAD as well as in MCF7 and T47D breast cancer cell lines. RESULTS: We found that the transition from 2 to 3D cultures of H460 and MCF7 cells is associated with significant changes in the expression of genes and proteins involved in metabolic reprogramming. In particular, we observed that 3D tumor spheroid growth implies the overexpression of ALDOC and ENO2 glycolytic enzymes concomitant with the enhanced consumption of glucose and fructose and the enhanced production of lactate. Transfection with siRNA against both ALDOC and ENO2 determined a significant reduction in lactate production, viability and size of 3D tumor spheroids produced by H460, HCC827, MCF7, and T47D cell lines. CONCLUSIONS: Our results show that anchorage-independent survival and growth of cancer cells are supported by changes in genes and proteins that drive glucose metabolism towards an enhanced lactate production. Notably, this finding is valid for all lung and breast cancer cell lines we have analyzed in different nutrient environmental conditions. broader Validation of this mechanism in other cancer cells of different origin will be necessary to broaden the role of ALDOC and ENO2 to other tumor types. Future in vivo studies will be necessary to assess the role of ALDOC and ENO2 in cancer metastasis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-023-02641-0. |
format | Online Article Text |
id | pubmed-10031988 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-100319882023-03-23 ALDOC- and ENO2- driven glucose metabolism sustains 3D tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis De Vitis, Claudia Battaglia, Anna Martina Pallocca, Matteo Santamaria, Gianluca Mimmi, Maria Chiara Sacco, Alessandro De Nicola, Francesca Gaspari, Marco Salvati, Valentina Ascenzi, Francesca Bruschini, Sara Esposito, Antonella Ricci, Giulia Sperandio, Eleonora Massacci, Alice Prestagiacomo, Licia Elvira Vecchione, Andrea Ricci, Alberto Sciacchitano, Salvatore Salerno, Gerardo French, Deborah Aversa, Ilenia Cereda, Cristina Fanciulli, Maurizio Chiaradonna, Ferdinando Solito, Egle Cuda, Giovanni Costanzo, Francesco Ciliberto, Gennaro Mancini, Rita Biamonte, Flavia J Exp Clin Cancer Res Research BACKGROUND: Metastases are the major cause of cancer-related morbidity and mortality. By the time cancer cells detach from their primary site to eventually spread to distant sites, they need to acquire the ability to survive in non-adherent conditions and to proliferate within a new microenvironment in spite of stressing conditions that may severely constrain the metastatic process. In this study, we gained insight into the molecular mechanisms allowing cancer cells to survive and proliferate in an anchorage-independent manner, regardless of both tumor-intrinsic variables and nutrient culture conditions. METHODS: 3D spheroids derived from lung adenocarcinoma (LUAD) and breast cancer cells were cultured in either nutrient-rich or -restricted culture conditions. A multi-omics approach, including transcriptomics, proteomics, and metabolomics, was used to explore the molecular changes underlying the transition from 2 to 3D cultures. Small interfering RNA-mediated loss of function assays were used to validate the role of the identified differentially expressed genes and proteins in H460 and HCC827 LUAD as well as in MCF7 and T47D breast cancer cell lines. RESULTS: We found that the transition from 2 to 3D cultures of H460 and MCF7 cells is associated with significant changes in the expression of genes and proteins involved in metabolic reprogramming. In particular, we observed that 3D tumor spheroid growth implies the overexpression of ALDOC and ENO2 glycolytic enzymes concomitant with the enhanced consumption of glucose and fructose and the enhanced production of lactate. Transfection with siRNA against both ALDOC and ENO2 determined a significant reduction in lactate production, viability and size of 3D tumor spheroids produced by H460, HCC827, MCF7, and T47D cell lines. CONCLUSIONS: Our results show that anchorage-independent survival and growth of cancer cells are supported by changes in genes and proteins that drive glucose metabolism towards an enhanced lactate production. Notably, this finding is valid for all lung and breast cancer cell lines we have analyzed in different nutrient environmental conditions. broader Validation of this mechanism in other cancer cells of different origin will be necessary to broaden the role of ALDOC and ENO2 to other tumor types. Future in vivo studies will be necessary to assess the role of ALDOC and ENO2 in cancer metastasis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-023-02641-0. BioMed Central 2023-03-22 /pmc/articles/PMC10031988/ /pubmed/36945054 http://dx.doi.org/10.1186/s13046-023-02641-0 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 De Vitis, Claudia Battaglia, Anna Martina Pallocca, Matteo Santamaria, Gianluca Mimmi, Maria Chiara Sacco, Alessandro De Nicola, Francesca Gaspari, Marco Salvati, Valentina Ascenzi, Francesca Bruschini, Sara Esposito, Antonella Ricci, Giulia Sperandio, Eleonora Massacci, Alice Prestagiacomo, Licia Elvira Vecchione, Andrea Ricci, Alberto Sciacchitano, Salvatore Salerno, Gerardo French, Deborah Aversa, Ilenia Cereda, Cristina Fanciulli, Maurizio Chiaradonna, Ferdinando Solito, Egle Cuda, Giovanni Costanzo, Francesco Ciliberto, Gennaro Mancini, Rita Biamonte, Flavia ALDOC- and ENO2- driven glucose metabolism sustains 3D tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis |
title | ALDOC- and ENO2- driven glucose metabolism sustains 3D tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis |
title_full | ALDOC- and ENO2- driven glucose metabolism sustains 3D tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis |
title_fullStr | ALDOC- and ENO2- driven glucose metabolism sustains 3D tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis |
title_full_unstemmed | ALDOC- and ENO2- driven glucose metabolism sustains 3D tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis |
title_short | ALDOC- and ENO2- driven glucose metabolism sustains 3D tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis |
title_sort | aldoc- and eno2- driven glucose metabolism sustains 3d tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10031988/ https://www.ncbi.nlm.nih.gov/pubmed/36945054 http://dx.doi.org/10.1186/s13046-023-02641-0 |
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