PMID- 20683396
OWN - NLM
STAT- MEDLINE
DCOM- 20101015
LR  - 20211020
IS  - 1525-1438 (Electronic)
IS  - 1048-891X (Linking)
VI  - 20
IP  - 6
DP  - 2010 Aug
TI  - Chemotherapy induces macrophage chemoattractant protein-1 production in ovarian 
      cancer.
PG  - 918-25
LID - 10.1111/IGC.0b013e3181e5c442 [doi]
AB  - 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.
FAU - Geller, Melissa A
AU  - Geller MA
AD  - Department of Obstetrics, Gynecology and Women's Health, Division of Gynecologic 
      Oncology, University of Minnesota, Minneapolis, MN 55455, USA. gelle005@umn.edu
FAU - Bui-Nguyen, Tri M
AU  - Bui-Nguyen TM
FAU - Rogers, Lisa M
AU  - Rogers LM
FAU - Ramakrishnan, Sundaram
AU  - Ramakrishnan S
LA  - eng
GR  - R01 CA114340/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - England
TA  - Int J Gynecol Cancer
JT  - International journal of gynecological cancer : official journal of the 
      International Gynecological Cancer Society
JID - 9111626
RN  - 0 (Chemokine CCL2)
RN  - BG3F62OND5 (Carboplatin)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Animals
MH  - Antineoplastic Combined Chemotherapy Protocols/*pharmacology
MH  - Carboplatin/pharmacology
MH  - Cell Line, Tumor/drug effects/metabolism
MH  - Chemokine CCL2/biosynthesis/*drug effects
MH  - Disease Models, Animal
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Macrophages/*drug effects/metabolism/pathology
MH  - Mice
MH  - Mice, Nude
MH  - Mitogen-Activated Protein Kinases/analysis/*metabolism
MH  - Ovarian Neoplasms/*drug therapy/*metabolism/pathology
MH  - Paclitaxel/pharmacology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sensitivity and Specificity
MH  - Signal Transduction/drug effects/genetics
MH  - Up-Regulation
EDAT- 2010/08/05 06:00
MHDA- 2010/10/16 06:00
CRDT- 2010/08/05 06:00
PHST- 2010/08/05 06:00 [entrez]
PHST- 2010/08/05 06:00 [pubmed]
PHST- 2010/10/16 06:00 [medline]
AID - 00009577-201008000-00003 [pii]
AID - 10.1111/IGC.0b013e3181e5c442 [doi]
PST - ppublish
SO  - Int J Gynecol Cancer. 2010 Aug;20(6):918-25. doi: 10.1111/IGC.0b013e3181e5c442.