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

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

Abstract

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.