Open AccessEnhancement of paclitaxel and carboplatin therapies by CCL2 blockade in ovarian cancers
Author(s) -
Moisan Francois,
Francisco Edgar B.,
Brozovic Anamaria,
Duran George E.,
Wang Yan C.,
Chaturvedi Shalini,
Seetharam Shobha,
Snyder Linda A.,
Doshi Parul,
Sikic Branimir I.
Publication year - 2014
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1016/j.molonc.2014.03.016
Subject(s) - carboplatin , paclitaxel , ovarian cancer , ccl2 , blockade , cancer research , chemotherapy , medicine , chemokine , pharmacology , stromal cell , cancer , oncology , receptor , cisplatin
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.