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

Moisan, François; Francisco, E. Brian; Brozović, Anamaria; Durán, George E.; Wang, Yan C.; Chaturvedi, Shalini; Seetharam, Shobha; Snyder, Linda A.; Doshi, Parul; Šikić, Branimir I.

doi:10.1016/j.molonc.2014.03.016

Cited by 99 publications

(73 citation statements)

References 22 publications

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“…In our animal model, we examined the expression of metastasis‐related molecules by knockdown of IL‐33. Reportedly, CCL2 has the ability to promote invasion and migration in prostatic carcinoma and ovarian carcinoma . Interleukin‐33 knockdown strongly downregulated CCL2, which could partly explain why IL‐33 knockdown impacted the reduced invasive capacity of ESCC cells.…”

Section: Discussionmentioning

confidence: 98%

Interleukin‐33‐nuclear factor‐κB‐CCL2 signaling pathway promotes progression of esophageal squamous cell carcinoma by directing regulatory T cells

Lian

Luo

et al. 2020

Cancer Science

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Esophageal cancer is currently one of the most fatal cancers. However, there is no effective treatment. Increasing evidence suggests that interleukin (IL)‐33 has a significant role in tumor progression and metastasis. Currently, the underlying cellular and molecular mechanism of IL‐33 in promoting esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we investigated whether IL‐33 could induce the epithelial‐mesenchymal transition (EMT) in ESCC. Interleukin‐33 expression was examined in ESCC and corresponding adjacent normal tissues by immunohistochemistry and quantitative real‐time PCR experiments. Elevated IL‐33 levels were observed in ESCC tissues. Further in vitro experiments were undertaken to elucidate the effect of IL‐33 on migration and invasion in KYSE‐450 and Eca‐109 esophageal cancer cells. Knockdown of IL‐33 decreased the metastasis and invasion capacity in esophageal cancer cells, whereas IL‐33 overexpression showed the opposite effect. We then screened CCL2 which is a downstream molecule of IL‐33, and proved that IL‐33 could promote tumor development and metastasis by recruiting regulatory T cells (Tregs) through CCL2, and IL‐33 regulated the expression of CCL2 through transforming growth factor‐β in Treg cells. Knockdown of IL‐33 decreased the development of human ESCC xenografts in BALB/c nude mice. Collectively, we found that the IL‐33/nuclear factor‐κB/CCL2 pathway played an essential role in human ESCC progress. Hence, IL‐33 should be considered as an effective therapy target for ESCC.

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Section: Discussionmentioning

confidence: 98%

Interleukin‐33‐nuclear factor‐κB‐CCL2 signaling pathway promotes progression of esophageal squamous cell carcinoma by directing regulatory T cells

Lian

Luo

et al. 2020

Cancer Science

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“…with 5–10 × 10 6 GLF-transduced GFP(+) OVCAR-3 parental or OVCAR-3/TP variant cells and imaged twice weekly (Moisan et al , 2014). At each time point, all mice were injected I.P.…”

Section: Methodsmentioning

confidence: 99%

Decreased levels of baseline and drug-induced tubulin polymerisation are hallmarks of resistance to taxanes in ovarian cancer cells and are associated with epithelial-to-mesenchymal transition

et al. 2017

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Background:ABCB1 expression is uncommon in ovarian cancers in the clinical setting so we investigated non-MDR mechanisms of resistance to taxanes.Methods:We established eight taxane-resistant variants from the human ovarian carcinoma cell lines A2780/1A9, ES-2, MES-OV and OVCAR-3 by selection with paclitaxel or docetaxel, with counter-selection by the transport inhibitor valspodar.Results:Non-MDR taxane resistance was associated with reduced intracellular taxane content compared to parental controls, and cross-resistance to other microtubule stabilising drugs. Collateral sensitivity to depolymerising agents (vinca alkaloids and colchicine) was observed with increased intracellular vinblastine. These variants exhibited marked decreases in basal tubulin polymer and in tubulin polymerisation in response to taxane exposure. TUBB3 content was increased in 6 of the 8 variants. We profiled gene expression of the parental lines and resistant variants, and identified a transcriptomic signature with two highly significant networks built around FN1 and CDKN1A that are associated with cell adhesion, cell-to-cell signalling, and cell cycle regulation. miR-200 family members miR-200b and miR-200c were downregulated in resistant cells, associated with epithelial to mesenchymal transition (EMT), with increased VIM, FN1, MMP2 and/or MMP9.Conclusions:These alterations may serve as biomarkers for predicting taxane effectiveness in ovarian cancer and should be considered as therapeutic targets.

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“…Two parental human serous ovarian carcinoma cell line were utilized: OVCAR‐3 (American Type Culture Collection, ATCC HTB‐161), and MES‐OV, developed by the Sikic Laboratory and submitted to the ATCC (Moisan et al., 2014). We developed the paclitaxel resistant variants, OVCAR‐3/TP and MES‐OV/TP, by step‐wise selection with paclitaxel and PSC‐833 (valspodar), an inhibitor of paclitaxel transport due to the inhibition of P‐glycoprotein function, in order to select for non‐transporter models of taxane resistance (Moisan et al., 2014). The resistant variants display an EMT phenotype and resistance to taxane drugs.…”

Section: Methodsmentioning

confidence: 99%

“…EMT is associated with the development of drug resistance in ovarian cancer cell models (Kanakkanthara and Miller, 2013), and these resistant variants exhibit decreased miR‐200 family content, a mesenchymal phenotype, and in some cases markedly increased growth in vivo compared to parental cell lines (Moisan et al., 2014). We explored the role of EMT/MET in response of two ovarian cancer cell lines, OVCAR‐3 and MES‐OV, and their taxane resistant variants, OVCAR‐3/TP and MES‐OV/TP to paclitaxel and carboplatin.…”

Section: Introductionmentioning

confidence: 99%

The miR‐200 family differentially regulates sensitivity to paclitaxel and carboplatin in human ovarian carcinoma OVCAR‐3 and MES‐OV cells

et al. 2015

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We studied the role of miRNA‐200 family members in cellular sensitivity to paclitaxel and carboplatin, using two ovarian cancer cell lines, OVCAR‐3 and MES‐OV, and their paclitaxel resistant variants OVCAR‐3/TP and MES‐OV/TP. Both resistant variants display a strong epithelial‐mesenchymal transition (EMT) phenotype, with marked decreases in expression of miR‐200c and miR‐141 in OVCAR‐3/TP, and down‐regulation of all five members of the miR‐200 family in MES‐OV/TP. Lentiviral transfection of inhibitors of miR‐200c or miR‐141 in parental OVCAR‐3 triggered EMT and rendered the cells resistant to paclitaxel and carboplatin. Conversely, the infection of OVCAR‐3/TP cells with retroviral particles carrying the miR‐200ab429 and 200c141 clusters triggered a partial mesenchymal to epithelial transition (MET). This partial MET was not sufficient to re‐sensitize OVCAR‐3/TP cells to paclitaxel. However, the miR‐200c/miR‐141 cluster transfectants became 6–8x resistant to carboplatin, an unexpected result, whereas miR‐200a/miR‐200b/miR‐429 had no effect. Transfecting the OVCAR‐3/TP GFP cells with specific miRNA mimics confirmed these data. MiR‐200c and miR‐141 mimics conferred resistance to carboplatin in MES‐OV/TP cells, similar to OVCAR‐3/TP, but sensitized MES‐OV to paclitaxel. Several genes involved in balancing oxidative stress were altered in OVCAR‐3/TP 200c141 cells compared to controls. The miR‐200 family plays major, cell‐context dependent roles in regulating EMT and sensitivity to carboplatin and paclitaxel in OVCAR‐3 and MES‐OV cells.

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

Cited by 99 publications

References 22 publications

Interleukin‐33‐nuclear factor‐κB‐CCL2 signaling pathway promotes progression of esophageal squamous cell carcinoma by directing regulatory T cells

Interleukin‐33‐nuclear factor‐κB‐CCL2 signaling pathway promotes progression of esophageal squamous cell carcinoma by directing regulatory T cells

Decreased levels of baseline and drug-induced tubulin polymerisation are hallmarks of resistance to taxanes in ovarian cancer cells and are associated with epithelial-to-mesenchymal transition

The miR‐200 family differentially regulates sensitivity to paclitaxel and carboplatin in human ovarian carcinoma OVCAR‐3 and MES‐OV cells

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