M2-Type Macrophages and Cancer-Associated Fibroblasts Combine to Promote Colorectal Cancer Liver Metastases

IF 2.7 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY OncoTargets and therapy Pub Date : 2024-03-26 DOI:10.2147/ott.s447502

Yunpeng Feng, Shifeng Qiao, Jie Chen, Xin Wen, Yanlei Chen, Xiaoyu Song, Jiaxin Xu, Xiucheng Qiao, Jing Yang, Shenshen Zhang, Yang Feng, Yu Gao

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Abstract

Purpose: This research explored the association between CD163-labeled M2-type macrophages and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) of 38 colorectal cancer (CRC) liver metastases. In addition, we investigated the correlation differences between M2-type macrophages and CAFs in the tumor microenvironments of 38 primary colorectal cancer patients with confirmed liver metastases and 946 colorectal cancer patients, as well as possible mechanisms of action between the two cells.
Methods: The Immunohistochemistry (IHC) method was applied to detect the expression levels of M2-type macrophages and CAFs in the tissues of 984 cases of CRC and to analyze the correlation between M2-type macrophages and CAFs in colorectal cancer tissues. The IHC method was also applied to detect the expression levels of M2-type macrophages and CAFs in the liver metastases of 38 cases of CRC in the experimental group and to analyze the correlation between the two cells in liver metastases.
Results: 1. M2-type macrophages and CAFs expression were significantly higher in 38 primary colorectal cancer patients compared to 946 controls, and the expression of M2-type macrophages was significantly positively correlated with CAFs. 2. In 984 CRC cases, M2-type macrophages and CAFs expression levels were significantly higher in the cancer tissues than in the paired paracancerous tissues. 3. The expression levels of M2-type macrophages and CAFs in primary colorectal cancer were significantly higher in the experimental group than in colorectal cancer tissues without distant metastasis.
Conclusion: M2-type macrophages and CAFs are involved in the development of the colorectal cancer tumor microenvironment, and their interaction influences the initiation and progression of liver metastasis in colorectal cancer. It may provide new clinical ideas for early diagnosis of CRC liver metastases and searching for immune targets.

Keywords: M2-type macrophages, cancer-associated fibroblasts, colorectal cancer, liver metastasis

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M2型巨噬细胞和癌症相关成纤维细胞共同促进结直肠癌肝转移

目的：本研究探讨了38例结直肠癌（CRC）肝转移灶的肿瘤微环境（TME）中CD163标记的M2型巨噬细胞与癌相关成纤维细胞（CAFs）之间的关联。此外，我们还研究了 38 例确诊肝转移的原发性结直肠癌患者和 946 例结直肠癌患者肿瘤微环境中 M2 型巨噬细胞和 CAFs 的相关性差异，以及两种细胞之间可能的作用机制：方法：采用免疫组化（IHC）方法检测984例CRC组织中M2型巨噬细胞和CAFs的表达水平，并分析M2型巨噬细胞和CAFs在结直肠癌组织中的相关性。同时应用IHC方法检测实验组38例CRC肝转移灶中M2型巨噬细胞和CAFs的表达水平，并分析两种细胞在肝转移灶中的相关性：1.38例原发性结直肠癌患者的M2型巨噬细胞和CAFs的表达量明显高于946例对照组，且M2型巨噬细胞的表达量与CAFs的表达量呈显著正相关。2.在 984 例 CRC 中，癌组织中 M2- 型巨噬细胞和 CAFs 的表达水平明显高于配对的癌旁组织。3.3. 实验组原发性结直肠癌中 M2 型巨噬细胞和 CAFs 的表达水平明显高于无远处转移的结直肠癌组织：结论：M2型巨噬细胞和CAFs参与结直肠癌肿瘤微环境的形成，其相互作用影响结直肠癌肝转移的发生和发展。这可能为早期诊断 CRC 肝转移和寻找免疫靶点提供新的临床思路：M2型巨噬细胞癌相关成纤维细胞大肠癌肝转移

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来源期刊

OncoTargets and therapy BIOTECHNOLOGY & APPLIED MICROBIOLOGY-ONCOLOGY

CiteScore

9.70

自引率

0.00%

发文量

221

审稿时长

1 months

期刊介绍： OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer. The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype. Specific topics covered by the journal include: -Novel therapeutic targets and innovative agents -Novel therapeutic regimens for improved benefit and/or decreased side effects -Early stage clinical trials Further considerations when submitting to OncoTargets and Therapy: -Studies containing in vivo animal model data will be considered favorably. -Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines. -Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples. -Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Single nucleotide polymorphism (SNP) studies will not be considered.