Reference - Detail
| RRC ID | 44273 |
|---|---|
| Author | Mano Y, Aishima S, Fujita N, Tanaka Y, Kubo Y, Motomura T, Taketomi A, Shirabe K, Maehara Y, Oda Y. |
| Title | Tumor-associated macrophage promotes tumor progression via STAT3 signaling in hepatocellular carcinoma. |
| Journal | Pathobiology |
| Abstract |
OBJECTIVE:Signal transducer and activator of transcription 3 (STAT3) is activated in hepatocellular carcinoma (HCC), and tumor-associated macrophage plays an important role in tumor progression. Therefore, we examined STAT3 activation, cytokine expression and infiltration of tumor-associated macrophages in resected HCCs as well as the alteration of cell growth and migration by cytokine stimulation in HCC cell lines. METHODS:Immunohistochemical staining of phosphorylated STAT3 (pSTAT3), CD163, interleukin (IL)-6, Ki-67 and Bcl-XL was performed for 101 cases of resected HCC, and correlations between pSTAT3 staining and clinicopathological findings were analyzed. In HCC cell lines (PLC/PRF/5 and Huh7), cell proliferation and migration by IL-6 stimulation and S3I-201 (STAT3 inhibitor) treatment were analyzed. RESULTS:In HCC specimens, the pSTAT3-positive group showed high levels of α-fetoprotein (p = 0.0276), large tumor size (p = 0.0092), frequent intrahepatic metastasis (p = 0.0214), high Ki-67 (p = 0.0002) and Bcl-XL (p = 0.0001), poor prognosis (p = 0.0234), and high recurrence rate (p = 0.0003). CD163-positive cells were frequently observed in the pSTAT3-positive group (p = 0.0013). In two HCC cell lines, IL-6 stimulation promoted cell proliferation and migration via the STAT3 phosphorylation, and S3I-201 inhibited this activation. CONCLUSIONS:STAT3 activation was correlated with aggressive behavior of HCC and may be mediated via tumor-associated macrophage. We expect that STAT3 signaling and tumor-associated macrophages can be attractive therapeutic targets in HCC patients. |
| Volume | 80(3) |
| Pages | 146-54 |
| Published | 2013-1-1 |
| DOI | 10.1159/000346196 |
| PII | 000346196 |
| PMID | 23364389 |
| MeSH | Carcinoma, Hepatocellular / immunology Carcinoma, Hepatocellular / metabolism* Carcinoma, Hepatocellular / pathology Disease Progression Female Humans Immunoblotting Immunohistochemistry Liver Neoplasms / immunology Liver Neoplasms / metabolism* Liver Neoplasms / pathology Macrophages / immunology Macrophages / metabolism* Male Middle Aged STAT3 Transcription Factor / metabolism* Signal Transduction / physiology* |
| IF | 1.985 |
| Times Cited | 52 |
| WOS Category | PATHOLOGY CELL BIOLOGY |
| Resource | |
| Human and Animal Cells | HuH-7 |