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http://ir.nhri.org.tw/handle/3990099045/3036
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| Title: | Up-regulation of tumor interleukin-8 expression by infiltrating macrophages: Its correlation with tumor angiogenesis and patient survival in non-small cell lung cancer |
| Authors: | Chen, JJW;Yao, PL;Yuan, A;Hong, TM;Shun, CT;Kuo, ML;Lee, YC;Yang, PC |
| Contributors: | National Institute of Cancer Research |
| Abstract: | Purpose: To evaluate the interaction between tumor-infiltrating macrophages and cancer cells and its effect on the expression of a potent angiogenic factor, interleukin-8 (IL-8), tumor angiogenesis, and patient outcome in non-small cell lung cancer (NSCLC). Experimental Design: We measured tumor IL-8 mRNA expression (by real-time quantitative reverse transcription-PCR), intratumor microvessel counts, and tumor-infiltrating macrophage density (by immunohistochemical staining) in 35 NSCLC surgical specimens and correlated with the patient's clinical outcome. We then investigated the interaction between macrophages (cell line THP-1) and six different human cancer cell lines (four NSCLCs, one osteosarcoma, and one hepatoma) and its effect on IL-8 mRNA expression using a macrophage/cancer cell coculture system, IL-8 mRNA expression in lung cancer cells, and macrophages being measured separately after coculture in the presence or absence of six anti-inflammatory agents, i.e., pentoxifylline, aspirin, indomethacin, dexamethasone, celecoxib (a selective cyclooxygenase-2 inhibitor), and pyrrolidine dithiocarbamate, a specific nuclear factor kappaB (NF-kappaB) inhibitor. NF-kappaB transcriptional activity and protein levels were measured by reporter gene assay and Western blot. Results: The tumor-infiltrating macrophage density correlated significantly and positively with tumor IL-8 mRNA expression and intratumor microvessel counts and significantly and negatively with patient survival. In addition, after cell-cell interaction in cancer cell:macrophage cocultures, marked IL-8 mRNA expression was induced in lung cancer cells (similar to270-fold) and, to a lesser degree, in macrophages (4.5-fold). The increase in IL-8 mRNA expression correlated with the in vitro metastatic potential of the cancer cells. All six anti-inflammatory agents suppressed induction of IL-8 mRNA expression in lung cancer cells by >90%, four (pentoxifylline, celecoxib, pyrrolidine dithiocarbamate, and dexamethasone) having a dose-dependent effect. NF-kappaB transcriptional regulation and protein levels were simultaneously increased in the nuclei of cancer cells in macrophage/cancer cell cocultures, this effect also being suppressed by all six anti-inflammatory agents. Conclusions: The interaction between infiltrating macrophages and cancer cells up-regulates IL-8 mRNA expression, especially in the cancer cells; this may contribute greatly to the increased tumor angiogenesis and adverse outcome in NSCLC patients with a high density of tumor-infiltrating macrophages. Anti-inflammatory agents can suppress the induction of IL-8 mRNA expression seen in lung cancer cells after coculture with macrophages, and this suppression is mediated, in part, through the NF-kappaB pathway. |
| Keywords: | Oncology |
| Date: | 2003-02 |
| Relation: | Clinical Cancer Research. 2003 Feb;9(2):729-737. |
| Link to: | http://clincancerres.aacrjournals.org/cgi/content/abstract/9/2/729 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1078-0432&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000180840200028 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0037314662 |
| Appears in Collections: | [其他] 期刊論文
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| 000180840200028.pdf | | 256Kb | Adobe PDF | 313 | View/Open |
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