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结直肠癌细胞作用下单核细胞的蛋白质组学全景。

The Proteomic Landscape of Monocytes in Response to Colorectal Cancer Cells.

机构信息

Peking University Fifth School of Clinical Medicine, Beijing 100730, China.

Center of Biotherapy, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China.

出版信息

J Proteome Res. 2024 Sep 6;23(9):4067-4081. doi: 10.1021/acs.jproteome.4c00400. Epub 2024 Aug 6.

DOI:10.1021/acs.jproteome.4c00400
PMID:39106312
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11385372/
Abstract

Colorectal cancer (CRC) involves a complex interaction between tumor cells and immune cells, notably monocytes, leading to immunosuppression. This study explored these interactions using in vitro coculture systems of THP-1 cells and CRC cell lines, employing quantitative proteomics to analyze protein changes in monocytes. Multiple analytical methods were utilized to delineate the altered proteomic landscape, identify key proteins, and their associated functional pathways for comprehensive data analysis. Differentially expressed proteins (DEPs) were selected and validated by cross-referencing them with publicly available TCGA and GEO data sets to explore their potential clinical significance. Our analysis identified 161 up-regulated and 130 down-regulated DEPs. The enrichment results revealed impairments in adhesion and innate immune functions in monocytes, potentially facilitating cancer progression. The down-regulation of FN1, THSB1, and JUN may contribute to these impairments. Furthermore, the overexpression of ADAMTSL4, PRAM1, GPNMB, and NPC2 on monocytes was associated with unfavorable prognostic outcomes in CRC patients, suggesting potential biomarkers or therapeutic targets. This study illustrated the proteomic landscape of monocytes in response to CRC cells, providing clues for future investigations of the crosstalk between cancer cells and monocytes within the tumor microenvironment.

摘要

结直肠癌（CRC）涉及肿瘤细胞与免疫细胞之间的复杂相互作用，特别是单核细胞，导致免疫抑制。本研究使用 THP-1 细胞和 CRC 细胞系的体外共培养系统来探索这些相互作用，采用定量蛋白质组学分析单核细胞中的蛋白质变化。利用多种分析方法描绘改变的蛋白质组学图谱，确定关键蛋白及其相关功能途径，进行全面数据分析。通过与公开的 TCGA 和 GEO 数据集交叉参考，选择和验证差异表达蛋白（DEPs），以探索其潜在的临床意义。我们的分析确定了 161 个上调和 130 个下调的 DEPs。富集结果表明单核细胞中黏附和固有免疫功能受损，可能促进癌症进展。FN1、THSB1 和 JUN 的下调可能促成了这些损伤。此外，单核细胞上 ADAMTSL4、PRAM1、GPNMB 和 NPC2 的过表达与 CRC 患者不良预后结局相关，提示可能的生物标志物或治疗靶点。本研究描绘了结直肠癌细胞作用下单核细胞的蛋白质组学图谱，为未来研究肿瘤微环境中癌细胞与单核细胞之间的串扰提供了线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1ab/11385372/a1ec188f1cf1/pr4c00400_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1ab/11385372/c3eac358275a/pr4c00400_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1ab/11385372/b38def6a0e76/pr4c00400_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1ab/11385372/9e68304dc3a5/pr4c00400_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1ab/11385372/b27304a9f0bc/pr4c00400_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1ab/11385372/8213c3b38cd4/pr4c00400_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1ab/11385372/e5b3f3ae709a/pr4c00400_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1ab/11385372/a1ec188f1cf1/pr4c00400_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1ab/11385372/c3eac358275a/pr4c00400_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1ab/11385372/b38def6a0e76/pr4c00400_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1ab/11385372/9e68304dc3a5/pr4c00400_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1ab/11385372/b27304a9f0bc/pr4c00400_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1ab/11385372/8213c3b38cd4/pr4c00400_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1ab/11385372/e5b3f3ae709a/pr4c00400_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1ab/11385372/a1ec188f1cf1/pr4c00400_0007.jpg

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aPEAR: an R package for autonomous visualization of pathway enrichment networks.APEAR：一个用于通路富集网络自主可视化的 R 包。
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THBS1-producing tumor-infiltrating monocyte-like cells contribute to immunosuppression and metastasis in colorectal cancer.产生 THBS1 的肿瘤浸润性单核细胞样细胞促进结直肠癌的免疫抑制和转移。
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