Enhancement of paclitaxel and carboplatin therapies by CCL2 blockade in ovarian cancers

Mol Oncol. 2014 Oct;8(7):1231-9. doi: 10.1016/j.molonc.2014.03.016. Epub 2014 Apr 18.

Abstract

Ovarian cancer is associated with a leukocyte infiltrate and high levels of chemokines such as CCL2. We tested the hypothesis that CCL2 inhibition can enhance chemotherapy with carboplatin and paclitaxel. Elevated CCL2 expression was found in three non-MDR paclitaxel resistant ovarian cancer lines ES-2/TP, MES-OV/TP and OVCAR-3/TP, compared to parental cells. Mice xenografted with these cells were treated with the anti-human CCL2 antibody CNTO 888 and the anti-mouse MCP-1 antibody C1142, with and without paclitaxel or carboplatin. Our results show an additive effect of CCL2 blockade on the efficacy of paclitaxel and carboplatin. This therapeutic effect was largely due to inhibition of mouse stromal CCL2. We show that inhibition of CCL2 can enhance paclitaxel and carboplatin therapy of ovarian cancer.

Keywords: CCL2; CCR2; Carboplatin; EMT; Paclitaxel; Resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / administration & dosage
  • Antibodies / immunology
  • Antibodies / pharmacology
  • Antibodies / therapeutic use*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Carboplatin / pharmacology
  • Carboplatin / therapeutic use*
  • Cell Line, Tumor
  • Chemokine CCL2 / antagonists & inhibitors*
  • Chemokine CCL2 / immunology
  • Drug Synergism
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / pathology
  • Ovary / drug effects
  • Ovary / immunology
  • Ovary / pathology
  • Paclitaxel / administration & dosage
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use*

Substances

  • Antibodies
  • Antineoplastic Agents
  • Chemokine CCL2
  • Carboplatin
  • Paclitaxel