Probing single-cell metabolism reveals prognostic value of highly metabolically active circulating stromal cells in prostate cancer.

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Abstrakt

Tytuł:: Probing single-cell metabolism reveals prognostic value of highly metabolically active circulating stromal cells in prostate cancer.
Autorzy:: Rivello F; Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, the Netherlands.
Matuła K; Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, the Netherlands.
Piruska A; Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, the Netherlands.
Smits M; Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.
Mehra N; Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.
Huck WTS; Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, the Netherlands. .
Źródło:: Science advances [Sci Adv] 2020 Sep 30; Vol. 6 (40). Date of Electronic Publication: 2020 Sep 30 (Print Publication: 2020).
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: Washington, DC : American Association for the Advancement of Science, [2015]-
MeSH Terms:: Neoplastic Cells, Circulating*/pathology
Prostatic Neoplasms*/diagnosis
Prostatic Neoplasms*/genetics
Cell Line, Tumor ; Endothelial Cells/metabolism ; Epithelial Cell Adhesion Molecule/genetics ; Epithelial Cell Adhesion Molecule/metabolism ; Humans ; Male ; Prognosis ; Stromal Cells ; Tumor Microenvironment/genetics
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Substance Nomenclature:: 0 (Epithelial Cell Adhesion Molecule)
Entry Date(s):: Date Created: 20201001 Date Completed: 20220413 Latest Revision: 20220413
Update Code:: 20240105
PubMed Central ID:: PMC7527228
DOI:: 10.1126/sciadv.aaz3849
PMID:: 32998889
: Czasopismo naukowe

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Despite their important role in metastatic disease, no general method to detect circulating stromal cells (CStCs) exists. Here, we present the Metabolic Assay-Chip (MA-Chip) as a label-free, droplet-based microfluidic approach allowing single-cell extracellular pH measurement for the detection and isolation of highly metabolically active cells (hm-cells) from the tumor microenvironment. Single-cell mRNA-sequencing analysis of the hm-cells from metastatic prostate cancer patients revealed that approximately 10% were canonical EpCAM + hm-CTCs, 3% were EpCAM - hm-CTCs with up-regulation of prostate-related genes, and 87% were hm-CStCs with profiles characteristic for cancer-associated fibroblasts, mesenchymal stem cells, and endothelial cells. Kaplan-Meier analysis shows that metastatic prostate cancer patients with more than five hm-cells have a significantly poorer survival probability than those with zero to five hm-cells. Thus, prevalence of hm-cells is a prognosticator of poor outcome in prostate cancer, and a potentially predictive and therapy response biomarker for agents cotargeting stromal components and preventing epithelial-to-mesenchymal transition.
(Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

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