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

doi:10.3389/fimmu.2022.1080501

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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	10 MB	Adobe Acrobat PDF	Read	Download
DOI Доступ к ресурсу на сайте издателя			10.3389/fimmu.2022.1080501

#моноциты

#колоректальный рак

#опухолеассоциированные макрофаги

#химиотерапия

#PFKFB3, ген

#транскриптом

#GeoMx DSP, программное обеспечение

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
Creator: Larionova, Irina V.
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Patysheva, Marina R.
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Iamshchikov, Pavel
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Kazakova, Elena O.
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Kazakova, Anna
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Rakina, Militsa A.
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Grigoryeva, Evgeniya S.
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Tarasova, Anna
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Afanasiev, Sergei
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Bezgodova, Natalia V.
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Kiselev, Artem
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Dobrodeev, Alexey Y.
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Kostromitskiy, Dmitriy
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Cherdyntseva, Nadezhda V.
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Kzhyshkowska, Julia G.
Date: 2022
DOI: 10.3389/fimmu.2022.1080501
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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collection(s): Химический факультет
Identifier: смотреть в электронном каталоге НБ ТГУ
Type: статьи в журналах
Source: Frontiers in immunology. 2022. Vol. 13. P. 1080501 (1-18)
Language: eng

Created: 22-11-2023

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Химический факультет 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