論文 - 詳細
| RRC ID | 83362 |
|---|---|
| 著者 | Ishihara N, Koma YI, Omori M, Komatsu S, Torigoe R, Yokoo H, Nakanishi T, Yamanaka K, Azumi Y, Tsukamoto S, Kodama T, Nishio M, Shigeoka M, Yokozaki H, Fukumoto T. |
| タイトル | Chemokine (C-C Motif) Ligand 2/CCR2/Extracellular Signal-Regulated Kinase Signal Induced through Cancer Cell-Macrophage Interaction Contributes to Hepatocellular Carcinoma Progression. |
| ジャーナル | Am J Pathol |
| Abstract |
Tumor-infiltrating macrophages, known as tumor-associated macrophages, play a crucial role in the tumor microenvironment. Herein, immunohistochemistry revealed that intratumoral CD68-positive macrophages are associated with poor prognosis and clinicopathologic factors in patients with hepatocellular carcinoma (HCC). Subsequently, an indirect co-culture system involving HCC cells and peripheral blood-derived macrophages was developed. cDNA microarray analysis revealed that chemokine (C-C motif) ligand 2 (CCL2) was highly expressed in HCC cells co-cultured with macrophages. CCL2 neutralization suppressed proliferation, migration, and phosphorylation of extracellular signal-regulated kinase (Erk) in HCC cells and macrophages enhanced through co-culture. In contrast, recombinant human CCL2 (rhCCL2) addition facilitated these malignant phenotypes and increased Erk phosphorylation levels in HCC cells and macrophages. The primary CCL2 receptor, CCR2, was expressed in HCC cells and macrophages and was up-regulated in co-cultured HCC cells. CCR2 inhibition suppressed malignant phenotypes and reduced phosphorylated levels of Erk enhanced by rhCCL2. Additionally, the inhibition of Erk signal suppressed rhCCL2-enhanced malignant phenotypes. Moreover, serum CCL2 levels were higher in patients with HCC than those in healthy donors. On the basis of immunohistochemistry, CCL2-positive cases with high CCR2 expression and phosphorylated Erk-positive cases exhibited poor survival outcomes. Therefore, CCL2 up-regulation through interactions between HCC cells and macrophages contributed to HCC progression, making the CCL2/CCR2/Erk signal a potential target for HCC treatment. |
| 巻・号 | 195(3) |
| ページ | 589-608 |
| 公開日 | 2025-3-1 |
| DOI | 10.1016/j.ajpath.2024.12.007 |
| PII | S0002-9440(24)00480-2 |
| PMID | 39756577 |
| PMC | PMC12179538 |
| MeSH | Carcinoma, Hepatocellular* / metabolism Carcinoma, Hepatocellular* / pathology Cell Communication Cell Line, Tumor Cell Movement Cell Proliferation Chemokine CCL2* / metabolism Coculture Techniques Disease Progression Extracellular Signal-Regulated MAP Kinases* / metabolism Female Humans Liver Neoplasms* / metabolism Liver Neoplasms* / pathology MAP Kinase Signaling System Macrophages* / metabolism Macrophages* / pathology Male Middle Aged Receptors, CCR2* / metabolism Signal Transduction Tumor Microenvironment Tumor-Associated Macrophages* / metabolism Tumor-Associated Macrophages* / pathology |
| IF | 3.491 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.7 |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2 HuH-7 |