巨噬细胞中表达的APOC1通过CCL2/CCL5促进结直肠癌肺转移

IF 4.8 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-04-07 DOI:10.1016/j.intimp.2025.114611

Fei Qin , Haosheng Zheng , Jiayan Wu , Zui Liu , Yuzhen Zheng , Xingping Yang , Junguo Chen , Weihao Deng , Ziyin Luo , Jian Tan , Weijie Cai , Bozhu Jian , Yushuai Zeng , Xianyu Qin , Hongying Liao

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引用次数: 0

摘要

转移是结直肠癌（CRC）死亡的主要原因，而肺是最常见的转移部位。然而，干预结直肠癌肺转移（CCPM）的有效靶点很少，特别是其独特的免疫微环境。在本研究中，16个基因被鉴定为CRC和CCPM之间核心CCPM相关差异表达基因（DEGs）。载脂蛋白C1 （APOC1）等3个基因与结直肠癌的预后、分期和转移有关。免疫组化结果显示，APOC1主要在巨噬细胞中表达，在CCPM中的表达高于CRC。同步性CCPM、分期越高、OS越差、无CCPM间期越高。在体外实验中，巨噬细胞中APOC1的敲低可减少CRC细胞的迁移、侵袭和上皮-间质转化。巨噬细胞中APOC1的敲低可显著降低CCL2和CCL5等趋化因子的分泌。表达APOC1的巨噬细胞的促转移作用被CCL2和CCL5抗体部分阻断。STAT3的激活是APOC1调控CCL2和CCL5的关键过程。在体内实验中，巨噬细胞中APOC1的下调可减少肺转移。综上所述，APOC1是ccpm相关的核心deg之一，与CRC的转移和生存有关。巨噬细胞表达APOC1通过APOC1- stat3 - ccl2 /CCL5轴促进CCPM。APOC1和表达APOC1的巨噬细胞在CCPM中发挥重要作用，可能是潜在的治疗靶点。

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APOC1 expressed in macrophages promotes the pulmonary metastasis of colorectal cancer via CCL2/CCL5

Metastasis is the main cause of death in colorectal cancer (CRC), and the lungs are common sites of metastasis. However, there is little effective target to intervene colorectal cancer pulmonary metastasis (CCPM), especially on its unique immune microenvironment. In this study, sixteen genes were identified as core CCPM-related differentially expressed genes (DEGs) between CRC and CCPM. Three genes including Apolipoprotein C1 (APOC1) were associated with prognosis, stage and metastasis of CRC. In immunohistochemistry, APOC1 was mainly expressed in macrophages, and expressed more in CCPM than CRC. Patients with synchronous CCPM, higher stage, poorer OS and CCPM-free interval tended to have higher expression. In experiments in vitro, knockdown of APOC1 in macrophages reduced the migration, invasion, and epithelial-mesenchymal transition of CRC cells. Knockdown of APOC1 in macrophages significantly decreased secretion of chemokines like CCL2 and CCL5. The pro-metastatic effect of macrophages expressing APOC1 was partially blocked by the antibodies of CCL2 and CCL5. Activation of STAT3 was a key process in APOC1's regulation of CCL2 and CCL5. In experiments in vivo, knockdown of APOC1 in macrophages reduced pulmonary metastasis. To conclude, APOC1 is one of core CCPM-related DEGs and associated with the metastasis and survival of CRC. Macrophages expressing APOC1 promote the CCPM by APOC1-STAT3-CCL2/CCL5 axis. APOC1 and macrophages expressing APOC1 play vital roles and may be potential therapeutic targets in CCPM.

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.