| Chemotherapy induces macrophage chemoattractant protein-1 production in ovarian cancer. | |
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MedLine Citation:
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PMID: 20683396 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: Tumor infiltrating macrophages play an important role in tumor progression. Macrophage chemoattractant protein-1 (MCP-1) is one of the major chemokines responsible for inducing macrophage migration. Our objective was to investigate chemotherapy-induced modulation of MCP-1 in ovarian cancer by investigating macrophage infiltration, tumor vascularity, and MCP-1 expression after chemotherapy exposure. METHODS: MA-148 ovarian cancer cells were treated with paclitaxel (43 pg/mL) and carboplatin (5 microg/mL) alone or in combination. Reverse transcription-polymerase chain reaction determined MCP-1 transcript levels and enzyme-linked immunosorbent assay evaluated MCP-1 protein production at multiple time points. The effect of kinase inhibitors on MCP-1 expression was investigated. In vivo MCP-1 production was examined in tumor-bearing mice and immunohistochemistry with fluorescein isothiocyanate conjugated anti-mouse F4/80 antibody, phycoerythrin-anti-CD31, and terminal deoxynucleotide transferase dUTP nick-end labeling assay were performed. RESULTS: Macrophage chemoattractant protein-1 transcript levels were up-regulated in MA-148 after treatment with paclitaxel and carboplatin individually and in combination. The greatest elevation was seen with combination therapy: 2.5-fold increase in the MCP-1 protein levels from baseline (P = 0.011) with the mitogen-activated protein kinase and janus kinases/signal transducers and activators of transcription pathways appearing to be involved in the regulation of MCP-1 production. In vivo mouse studies confirmed increased MCP-1 production after chemotherapy; however, there was no significant difference in macrophage, apoptosis, or vessel density. CONCLUSIONS: Macrophage chemoattractant protein-1 is up-regulated in ovarian cancer after chemotherapy in vitro and in vivo. Whether MCP-1 production is increased because of a stress-induced response or a scavenger response promoting macrophage infiltration remains unknown. Chemotherapy induction of MCP-1 in ovarian cancer suggests this chemokine plays an important role in the immune response occurring after chemotherapy exposure. |
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Authors:
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Melissa A Geller; Tri M Bui-Nguyen; Lisa M Rogers; Sundaram Ramakrishnan |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society Volume: 20 ISSN: 1525-1438 ISO Abbreviation: Int. J. Gynecol. Cancer Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-04 Completed Date: 2010-10-15 Revised Date: 2010-12-03 |
Medline Journal Info:
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Nlm Unique ID: 9111626 Medline TA: Int J Gynecol Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 918-25 Citation Subset: IM |
Affiliation:
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Department of Obstetrics, Gynecology and Women's Health, Division of Gynecologic Oncology, University of Minnesota, Minneapolis, MN 55455, USA. gelle005@umn.edu |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Combined Chemotherapy Protocols / pharmacology* Carboplatin / pharmacology Cell Line, Tumor / drug effects, metabolism Chemokine CCL2 / biosynthesis, drug effects* Disease Models, Animal Enzyme-Linked Immunosorbent Assay Female Humans Immunohistochemistry Macrophages / drug effects*, metabolism, pathology Mice Mice, Nude Mitogen-Activated Protein Kinases / analysis, metabolism* Ovarian Neoplasms / drug therapy*, metabolism*, pathology Paclitaxel / pharmacology Reverse Transcriptase Polymerase Chain Reaction Sensitivity and Specificity Signal Transduction / drug effects, genetics Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA114340-05/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chemokine CCL2; 33069-62-4/Paclitaxel; 41575-94-4/Carboplatin; EC 2.7.11.24/Mitogen-Activated Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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