title: Enhancement of paclitaxel and carboplatin therapies by CCL2 blockade in ovarian cancers.
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.
authors.affiliation: Stanford University, Stanford, CA 94305-5151, USA.
authors.forename: Francois
authors.initials: F
authors.lastname: Moisan
authors.affiliation: Stanford University, Stanford, CA 94305-5151, USA.
authors.forename: Edgar B
authors.initials: EB
authors.lastname: Francisco
authors.affiliation: Stanford University, Stanford, CA 94305-5151, USA.
authors.forename: Anamaria
authors.initials: A
authors.lastname: Brozovic
authors.affiliation: Stanford University, Stanford, CA 94305-5151, USA.
authors.forename: George E
authors.initials: GE
authors.lastname: Duran
authors.affiliation: Stanford University, Stanford, CA 94305-5151, USA.
authors.forename: Yan C
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Janssen Research and Development, LLC, Spring House, PA 19477, USA.
authors.forename: Shalini
authors.initials: S
authors.lastname: Chaturvedi
authors.affiliation: Janssen Research and Development, LLC, Spring House, PA 19477, USA.
authors.forename: Shobha
authors.initials: S
authors.lastname: Seetharam
authors.affiliation: Janssen Research and Development, LLC, Spring House, PA 19477, USA.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Snyder
authors.affiliation: Janssen Research and Development, LLC, Spring House, PA 19477, USA.
authors.forename: Parul
authors.initials: P
authors.lastname: Doshi
authors.affiliation: Stanford University, Stanford, CA 94305-5151, USA. Electronic address: brandy@stanford.edu.
authors.forename: Branimir I
authors.initials: BI
authors.lastname: Sikic
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000276:immunology; D004357:Drug Synergism; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D010053:Ovary / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D018932:Chemokine CCL2; D016190:Carboplatin; D017239:Paclitaxel
keywords: CCL2; CCR2; Carboplatin; EMT; Paclitaxel; Resistance