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Metabolic Alterations in Pancreatic Cancer Progression

Pancreatic cancer is the third leading cause of cancer-related deaths in the USA. Pancreatic tumors are characterized by enhanced glycolytic metabolism promoted by a hypoxic tumor microenvironment and a resultant acidic milieu. The metabolic reprogramming allows cancer cells to survive hostile micro...

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Autores principales: Vernucci, Enza, Abrego, Jaime, Gunda, Venugopal, Shukla, Surendra K., Dasgupta, Aneesha, Rai, Vikrant, Chaika, Nina, Buettner, Kyla, Illies, Alysha, Yu, Fang, Lazenby, Audrey J., Swanson, Benjamin J., Singh, Pankaj K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016676/
https://www.ncbi.nlm.nih.gov/pubmed/31861288
http://dx.doi.org/10.3390/cancers12010002
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author Vernucci, Enza
Abrego, Jaime
Gunda, Venugopal
Shukla, Surendra K.
Dasgupta, Aneesha
Rai, Vikrant
Chaika, Nina
Buettner, Kyla
Illies, Alysha
Yu, Fang
Lazenby, Audrey J.
Swanson, Benjamin J.
Singh, Pankaj K.
author_facet Vernucci, Enza
Abrego, Jaime
Gunda, Venugopal
Shukla, Surendra K.
Dasgupta, Aneesha
Rai, Vikrant
Chaika, Nina
Buettner, Kyla
Illies, Alysha
Yu, Fang
Lazenby, Audrey J.
Swanson, Benjamin J.
Singh, Pankaj K.
author_sort Vernucci, Enza
collection PubMed
description Pancreatic cancer is the third leading cause of cancer-related deaths in the USA. Pancreatic tumors are characterized by enhanced glycolytic metabolism promoted by a hypoxic tumor microenvironment and a resultant acidic milieu. The metabolic reprogramming allows cancer cells to survive hostile microenvironments. Through the analysis of the principal metabolic pathways, we identified the specific metabolites that are altered during pancreatic cancer progression in the spontaneous progression (KPC) mouse model. Genetically engineered mice exhibited metabolic alterations during PanINs formation, even before the tumor development. To account for other cells in the tumor microenvironment and to focus on metabolic adaptations concerning tumorigenic cells only, we compared the metabolic profile of KPC and orthotopic tumors with those obtained from KPC-tumor derived cell lines. We observed significant upregulation of glycolysis and the pentose phosphate pathway metabolites even at the early stages of pathogenesis. Other biosynthetic pathways also demonstrated a few common perturbations. While some of the metabolic changes in tumor cells are not detectable in orthotopic and spontaneous tumors, a significant number of tumor cell-intrinsic metabolic alterations are readily detectable in the animal models. Overall, we identified that metabolic alterations in precancerous lesions are maintained during cancer development and are largely mirrored by cancer cells in culture conditions.
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spelling pubmed-70166762020-02-28 Metabolic Alterations in Pancreatic Cancer Progression Vernucci, Enza Abrego, Jaime Gunda, Venugopal Shukla, Surendra K. Dasgupta, Aneesha Rai, Vikrant Chaika, Nina Buettner, Kyla Illies, Alysha Yu, Fang Lazenby, Audrey J. Swanson, Benjamin J. Singh, Pankaj K. Cancers (Basel) Article Pancreatic cancer is the third leading cause of cancer-related deaths in the USA. Pancreatic tumors are characterized by enhanced glycolytic metabolism promoted by a hypoxic tumor microenvironment and a resultant acidic milieu. The metabolic reprogramming allows cancer cells to survive hostile microenvironments. Through the analysis of the principal metabolic pathways, we identified the specific metabolites that are altered during pancreatic cancer progression in the spontaneous progression (KPC) mouse model. Genetically engineered mice exhibited metabolic alterations during PanINs formation, even before the tumor development. To account for other cells in the tumor microenvironment and to focus on metabolic adaptations concerning tumorigenic cells only, we compared the metabolic profile of KPC and orthotopic tumors with those obtained from KPC-tumor derived cell lines. We observed significant upregulation of glycolysis and the pentose phosphate pathway metabolites even at the early stages of pathogenesis. Other biosynthetic pathways also demonstrated a few common perturbations. While some of the metabolic changes in tumor cells are not detectable in orthotopic and spontaneous tumors, a significant number of tumor cell-intrinsic metabolic alterations are readily detectable in the animal models. Overall, we identified that metabolic alterations in precancerous lesions are maintained during cancer development and are largely mirrored by cancer cells in culture conditions. MDPI 2019-12-18 /pmc/articles/PMC7016676/ /pubmed/31861288 http://dx.doi.org/10.3390/cancers12010002 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vernucci, Enza
Abrego, Jaime
Gunda, Venugopal
Shukla, Surendra K.
Dasgupta, Aneesha
Rai, Vikrant
Chaika, Nina
Buettner, Kyla
Illies, Alysha
Yu, Fang
Lazenby, Audrey J.
Swanson, Benjamin J.
Singh, Pankaj K.
Metabolic Alterations in Pancreatic Cancer Progression
title Metabolic Alterations in Pancreatic Cancer Progression
title_full Metabolic Alterations in Pancreatic Cancer Progression
title_fullStr Metabolic Alterations in Pancreatic Cancer Progression
title_full_unstemmed Metabolic Alterations in Pancreatic Cancer Progression
title_short Metabolic Alterations in Pancreatic Cancer Progression
title_sort metabolic alterations in pancreatic cancer progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016676/
https://www.ncbi.nlm.nih.gov/pubmed/31861288
http://dx.doi.org/10.3390/cancers12010002
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