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PFKFB3 overexpression in monocytes of patients with colon but not rectal cancer programs pro-tumor macrophages and is indicative for higher risk of tumor relapse

INTRODUCTION: Circulating monocytes are main source for tumor-associated macrophages (TAMs) that control tumor growth, angiogenesis, metastasis and therapy resistance. We raised the questions how monocyte programming is affected by growing tumors localized in colon and rectal sections, and how treat...

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Autores principales: Larionova, Irina, Patysheva, Marina, Iamshchikov, Pavel, Kazakova, Elena, Kazakova, Anna, Rakina, Militsa, Grigoryeva, Evgeniya, Tarasova, Anna, Afanasiev, Sergei, Bezgodova, Natalia, Kiselev, Artem, Dobrodeev, Alexey, Kostromitskiy, Dmitriy, Cherdyntseva, Nadezhda, Kzhyshkowska, Julia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9887047/
https://www.ncbi.nlm.nih.gov/pubmed/36733385
http://dx.doi.org/10.3389/fimmu.2022.1080501
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author Larionova, Irina
Patysheva, Marina
Iamshchikov, Pavel
Kazakova, Elena
Kazakova, Anna
Rakina, Militsa
Grigoryeva, Evgeniya
Tarasova, Anna
Afanasiev, Sergei
Bezgodova, Natalia
Kiselev, Artem
Dobrodeev, Alexey
Kostromitskiy, Dmitriy
Cherdyntseva, Nadezhda
Kzhyshkowska, Julia
author_facet Larionova, Irina
Patysheva, Marina
Iamshchikov, Pavel
Kazakova, Elena
Kazakova, Anna
Rakina, Militsa
Grigoryeva, Evgeniya
Tarasova, Anna
Afanasiev, Sergei
Bezgodova, Natalia
Kiselev, Artem
Dobrodeev, Alexey
Kostromitskiy, Dmitriy
Cherdyntseva, Nadezhda
Kzhyshkowska, Julia
author_sort Larionova, Irina
collection PubMed
description INTRODUCTION: Circulating monocytes are main source for tumor-associated macrophages (TAMs) that control tumor growth, angiogenesis, metastasis and therapy resistance. We raised the questions how monocyte programming is affected by growing tumors localized in colon and rectal sections, and how treatment onsets affect monocyte programming in the circulation. METHODS: Patients with rectal cancer and colon cancer were enrolled in the study. Peripheral blood monocytes were characterized by phenotypic analysis using flow cytometry, by transcriptomic analysis using RNA sequencing and by gene expression analysis using real-time RT-PCR. Phenotypic analysis was performed with IF/confocal microscopy. Spatial transcriptomic analysis was applied using GeoMX DSP-NGS. RESULTS: In patients with rectal cancer, increased amount of CCR2+ monocytes was indicative for the absence of both lymphatic and hematogenous metastasis. In contrast, in patients with colon cancer CD163+ monocytes were indicative for LN metastasis. NGS analysis identified tumor-specific transcriptional programming of monocytes in all CRC patients compared to healthy individuals. The key transcriptional difference between monocytes of patients with colon and rectal cancer was increased expression of PFKFB3, activator of glycolysis that is currently considered as therapy target for major solid cancers. PFKFB3-expressing monocyte-derived macrophages massively infiltrated tumor in colon. Nanostring technology identified correlation of PFKFB3 with amount and tumor-promoting properties of TAMs in colon but not in rectal cancer. PFKFB3 was indicative for tumor relapse specifically in colon cancer. DISCUSSION: Our findings provide essential argument towards CRC definition to cover two clinically distinct cancers – colon cancer and rectal cancer, that differentially interact with innate immunity.
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spelling pubmed-98870472023-02-01 PFKFB3 overexpression in monocytes of patients with colon but not rectal cancer programs pro-tumor macrophages and is indicative for higher risk of tumor relapse Larionova, Irina Patysheva, Marina Iamshchikov, Pavel Kazakova, Elena Kazakova, Anna Rakina, Militsa Grigoryeva, Evgeniya Tarasova, Anna Afanasiev, Sergei Bezgodova, Natalia Kiselev, Artem Dobrodeev, Alexey Kostromitskiy, Dmitriy Cherdyntseva, Nadezhda Kzhyshkowska, Julia Front Immunol Immunology INTRODUCTION: Circulating monocytes are main source for tumor-associated macrophages (TAMs) that control tumor growth, angiogenesis, metastasis and therapy resistance. We raised the questions how monocyte programming is affected by growing tumors localized in colon and rectal sections, and how treatment onsets affect monocyte programming in the circulation. METHODS: Patients with rectal cancer and colon cancer were enrolled in the study. Peripheral blood monocytes were characterized by phenotypic analysis using flow cytometry, by transcriptomic analysis using RNA sequencing and by gene expression analysis using real-time RT-PCR. Phenotypic analysis was performed with IF/confocal microscopy. Spatial transcriptomic analysis was applied using GeoMX DSP-NGS. RESULTS: In patients with rectal cancer, increased amount of CCR2+ monocytes was indicative for the absence of both lymphatic and hematogenous metastasis. In contrast, in patients with colon cancer CD163+ monocytes were indicative for LN metastasis. NGS analysis identified tumor-specific transcriptional programming of monocytes in all CRC patients compared to healthy individuals. The key transcriptional difference between monocytes of patients with colon and rectal cancer was increased expression of PFKFB3, activator of glycolysis that is currently considered as therapy target for major solid cancers. PFKFB3-expressing monocyte-derived macrophages massively infiltrated tumor in colon. Nanostring technology identified correlation of PFKFB3 with amount and tumor-promoting properties of TAMs in colon but not in rectal cancer. PFKFB3 was indicative for tumor relapse specifically in colon cancer. DISCUSSION: Our findings provide essential argument towards CRC definition to cover two clinically distinct cancers – colon cancer and rectal cancer, that differentially interact with innate immunity. Frontiers Media S.A. 2023-01-17 /pmc/articles/PMC9887047/ /pubmed/36733385 http://dx.doi.org/10.3389/fimmu.2022.1080501 Text en Copyright © 2023 Larionova, Patysheva, Iamshchikov, Kazakova, Kazakova, Rakina, Grigoryeva, Tarasova, Afanasiev, Bezgodova, Kiselev, Dobrodeev, Kostromitskiy, Cherdyntseva and Kzhyshkowska https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Larionova, Irina
Patysheva, Marina
Iamshchikov, Pavel
Kazakova, Elena
Kazakova, Anna
Rakina, Militsa
Grigoryeva, Evgeniya
Tarasova, Anna
Afanasiev, Sergei
Bezgodova, Natalia
Kiselev, Artem
Dobrodeev, Alexey
Kostromitskiy, Dmitriy
Cherdyntseva, Nadezhda
Kzhyshkowska, Julia
PFKFB3 overexpression in monocytes of patients with colon but not rectal cancer programs pro-tumor macrophages and is indicative for higher risk of tumor relapse
title PFKFB3 overexpression in monocytes of patients with colon but not rectal cancer programs pro-tumor macrophages and is indicative for higher risk of tumor relapse
title_full PFKFB3 overexpression in monocytes of patients with colon but not rectal cancer programs pro-tumor macrophages and is indicative for higher risk of tumor relapse
title_fullStr PFKFB3 overexpression in monocytes of patients with colon but not rectal cancer programs pro-tumor macrophages and is indicative for higher risk of tumor relapse
title_full_unstemmed PFKFB3 overexpression in monocytes of patients with colon but not rectal cancer programs pro-tumor macrophages and is indicative for higher risk of tumor relapse
title_short PFKFB3 overexpression in monocytes of patients with colon but not rectal cancer programs pro-tumor macrophages and is indicative for higher risk of tumor relapse
title_sort pfkfb3 overexpression in monocytes of patients with colon but not rectal cancer programs pro-tumor macrophages and is indicative for higher risk of tumor relapse
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9887047/
https://www.ncbi.nlm.nih.gov/pubmed/36733385
http://dx.doi.org/10.3389/fimmu.2022.1080501
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