The Role of Chemokine (C-C Motif) Ligand 7 (CCL7) in Hepatocellular Carcinoma: Expression, Function, and Mechanisms

IF 3.1 2区医学 Q2 ONCOLOGY Cancer Medicine Pub Date : 2025-03-10 DOI:10.1002/cam4.70701

Yangkun Luo, Fei Wan, Zhao Zhang, Zujun Qin, Yongjun Ren

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Abstract

Aim

AHepatocellular carcinoma (HCC) is a malignant neoplasm characterized by a poor prognosis, with its incidence rising globally. Chemokine (C-C motif) ligand 7 (CCL7), a chemokine protein, has been implicated in the progression of various cancers. Nonetheless, the specific role of CCL7 in HCC has yet to be elucidated. This study seeks to examine the expression and functional role of CCL7 in the context of HCC.

Materials & Methods

Western blot and immunohistochemistry were used to detect the expression of CCL7 in HCC tissues and cell lines. Cell Counting Kit 8 (CCK8) assay, clonogenic assay, and transwell assay were performed to examine the effects of CCL7 on SNU-878 cells. Immunofluorescence was used to analyze the expression of proteins associated with epithelial interstitial transformation (EMT). Western blot was used to detect the activation of the PI3K/AKT pathway. In vivo tumorigenesis experiments were performed to assess the role of CCL7 in HCC tumorigenesis.

Results

The results showed that the expression of CCL7 was up-regulated in HCC tissues, and exogenous CCL7 promoted the proliferation, migration, invasion, and EMT of SNU-878 cells and VEGF secretion by SNU-878 cells. Furthermore, CCL7 stimulated the activation of the PI3K/AKT pathway. Further analysis revealed that CCL7 targeted CCR1 and CCR2 to enhance the growth, and metastasis of SNU-878 cells and VEGF secretion by SNU-878 cells. CCR1/CCR2 silencing prevented CCL7 from activating the PI3K/AKT signaling pathway in SNU-878 cells. Moreover, CCL7 facilitated HCC tumorigenesis and VEGF expression in vivo.

Conclusion

Our findings indicate that CCL7 plays a promoting role in HCC growth and tumorigenesis, potentially via targeting CCR1 and CCR2 and activating the PI3K/AKT pathway.

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趋化因子（C-C Motif）配体7 （CCL7）在肝细胞癌中的作用：表达、功能和机制

目的肝细胞癌（HCC）是一种预后较差的恶性肿瘤，其发病率在全球范围内呈上升趋势。趋化因子（C-C基序）配体7 （CCL7）是一种趋化因子蛋白，与多种癌症的进展有关。尽管如此，CCL7在HCC中的具体作用尚未阐明。本研究旨在探讨CCL7在HCC中的表达和功能作用。材料,方法采用Western blot和免疫组化方法检测CCL7在肝癌组织和细胞系中的表达。采用细胞计数试剂盒8 （CCK8）法、克隆生成法和transwell法检测CCL7对SNU-878细胞的影响。免疫荧光法分析上皮间质转化（epithelial interstitial transformation， EMT）相关蛋白的表达。Western blot检测PI3K/AKT通路的激活情况。通过体内肿瘤发生实验来评估CCL7在HCC肿瘤发生中的作用。结果CCL7在HCC组织中表达上调，外源性CCL7促进了SNU-878细胞的增殖、迁移、侵袭、EMT以及SNU-878细胞的VEGF分泌。此外，CCL7刺激了PI3K/AKT通路的激活。进一步分析发现，CCL7靶向CCR1和CCR2可促进SNU-878细胞的生长、转移和VEGF的分泌。CCR1/CCR2沉默可阻止CCL7激活SNU-878细胞中的PI3K/AKT信号通路。此外，CCL7促进了HCC的发生和VEGF在体内的表达。结论CCL7可能通过靶向CCR1和CCR2并激活PI3K/AKT通路，在HCC生长和肿瘤发生中发挥促进作用。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.