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Single Cell Analysis Reveals Reciprocal Tumor-Macrophage Intercellular Communications Related with Metabolic Reprogramming in Stem-like Gastric Cancer

Metabolic alterations and direct cell–cell interactions in the tumor microenvironment (TME) affect the prognostic molecular landscape of tumors; thus, it is imperative to investigate metabolic activity at the single-cell level rather than in bulk samples to understand the high-resolution mechanistic...

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Autores principales: Sung, Ji-Yong, Cheong, Jae-Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368184/
https://www.ncbi.nlm.nih.gov/pubmed/35954218
http://dx.doi.org/10.3390/cells11152373
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author Sung, Ji-Yong
Cheong, Jae-Ho
author_facet Sung, Ji-Yong
Cheong, Jae-Ho
author_sort Sung, Ji-Yong
collection PubMed
description Metabolic alterations and direct cell–cell interactions in the tumor microenvironment (TME) affect the prognostic molecular landscape of tumors; thus, it is imperative to investigate metabolic activity at the single-cell level rather than in bulk samples to understand the high-resolution mechanistic influences of cell-type specific metabolic pathway alterations on tumor cells. To investigate tumor metabolic reprogramming and intercellular communication at the single-cell level, we analyzed eighty-four metabolic pathways, seven metabolic signatures, and tumor-stroma cell interaction using 21,084 cells comprising gastric cancer and paired normal tissue. High EMT-score cells and stem-like subtype tumors showed elevated glycosaminoglycan metabolism, which was associated with poor patient outcome. Adenocarcinoma and macrophage cells had higher reactive oxidative species levels than the normal controls; they largely constituted the highest stemness cluster. They were found to reciprocally communicate through the common ligand RPS19. Consequently, ligand-target regulated transcriptional reprogramming resulted in HS6ST2 expression in adenocarcinoma cells and SERPINE1 expression in macrophages. Gastric cancer patients with increased SERPINE1 and HS6ST2 expression had unfavorable prognoses, suggesting these as potential drug targets. Our findings indicate that malignant stem-like/EMT cancer cell state might be regulated through reciprocal cancer cell-macrophage intercellular communication and metabolic reprogramming in the heterogeneous TME of gastric cancer at the single-cell level.
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spelling pubmed-93681842022-08-12 Single Cell Analysis Reveals Reciprocal Tumor-Macrophage Intercellular Communications Related with Metabolic Reprogramming in Stem-like Gastric Cancer Sung, Ji-Yong Cheong, Jae-Ho Cells Article Metabolic alterations and direct cell–cell interactions in the tumor microenvironment (TME) affect the prognostic molecular landscape of tumors; thus, it is imperative to investigate metabolic activity at the single-cell level rather than in bulk samples to understand the high-resolution mechanistic influences of cell-type specific metabolic pathway alterations on tumor cells. To investigate tumor metabolic reprogramming and intercellular communication at the single-cell level, we analyzed eighty-four metabolic pathways, seven metabolic signatures, and tumor-stroma cell interaction using 21,084 cells comprising gastric cancer and paired normal tissue. High EMT-score cells and stem-like subtype tumors showed elevated glycosaminoglycan metabolism, which was associated with poor patient outcome. Adenocarcinoma and macrophage cells had higher reactive oxidative species levels than the normal controls; they largely constituted the highest stemness cluster. They were found to reciprocally communicate through the common ligand RPS19. Consequently, ligand-target regulated transcriptional reprogramming resulted in HS6ST2 expression in adenocarcinoma cells and SERPINE1 expression in macrophages. Gastric cancer patients with increased SERPINE1 and HS6ST2 expression had unfavorable prognoses, suggesting these as potential drug targets. Our findings indicate that malignant stem-like/EMT cancer cell state might be regulated through reciprocal cancer cell-macrophage intercellular communication and metabolic reprogramming in the heterogeneous TME of gastric cancer at the single-cell level. MDPI 2022-08-02 /pmc/articles/PMC9368184/ /pubmed/35954218 http://dx.doi.org/10.3390/cells11152373 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sung, Ji-Yong
Cheong, Jae-Ho
Single Cell Analysis Reveals Reciprocal Tumor-Macrophage Intercellular Communications Related with Metabolic Reprogramming in Stem-like Gastric Cancer
title Single Cell Analysis Reveals Reciprocal Tumor-Macrophage Intercellular Communications Related with Metabolic Reprogramming in Stem-like Gastric Cancer
title_full Single Cell Analysis Reveals Reciprocal Tumor-Macrophage Intercellular Communications Related with Metabolic Reprogramming in Stem-like Gastric Cancer
title_fullStr Single Cell Analysis Reveals Reciprocal Tumor-Macrophage Intercellular Communications Related with Metabolic Reprogramming in Stem-like Gastric Cancer
title_full_unstemmed Single Cell Analysis Reveals Reciprocal Tumor-Macrophage Intercellular Communications Related with Metabolic Reprogramming in Stem-like Gastric Cancer
title_short Single Cell Analysis Reveals Reciprocal Tumor-Macrophage Intercellular Communications Related with Metabolic Reprogramming in Stem-like Gastric Cancer
title_sort single cell analysis reveals reciprocal tumor-macrophage intercellular communications related with metabolic reprogramming in stem-like gastric cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368184/
https://www.ncbi.nlm.nih.gov/pubmed/35954218
http://dx.doi.org/10.3390/cells11152373
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