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.
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-mouseF4/80 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.
Authors: Yan Li; Pavel Adamek; Haijun Zhang; Claudio Esteves Tatsui; Laurence D Rhines; Petra Mrozkova; Qin Li; Alyssa K Kosturakis; Ryan M Cassidy; Daniel S Harrison; Juan P Cata; Kenneth Sapire; Hongmei Zhang; Ross M Kennamer-Chapman; Abdul Basit Jawad; Andre Ghetti; Jiusheng Yan; Jiri Palecek; Patrick M Dougherty Journal: J Neurosci Date: 2015-09-30 Impact factor: 6.167
Authors: Locke D Uppendahl; Martin Felices; Laura Bendzick; Caitlin Ryan; Behiye Kodal; Peter Hinderlie; Kristin L M Boylan; Amy P N Skubitz; Jeffrey S Miller; Melissa A Geller Journal: Gynecol Oncol Date: 2019-01-15 Impact factor: 5.482
Authors: Sjoerd H van der Burg; Ramon Arens; Ferry Ossendorp; Thorbald van Hall; Cornelis J M Melief Journal: Nat Rev Cancer Date: 2016-03-11 Impact factor: 60.716
Authors: M Felices; S Chu; B Kodal; L Bendzick; C Ryan; A J Lenvik; K L M Boylan; H C Wong; A P N Skubitz; J S Miller; M A Geller Journal: Gynecol Oncol Date: 2017-02-22 Impact factor: 5.482