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

IF 2.9 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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引用次数: 0

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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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.