Anti-CD44 monoclonal antibody, clone 157-4D12

Aims: Cancer-derived exosomes carrying tumor-derived molecules such as miRNAs and proteins related to various phenotypes have been detected in both the bloodstream and other biofluids of patients with different cancers. Thus, our main purpose here was to determine the role of the exosomal microRNA-454 (miR-454) derived by MDA-MB-231 in self-renewal of cancer stem cells (CSCs) in ovarian cancer (OC). Materials and methods: Extraction of MDA-MB-231 cells-derived exosomes (231-derived exosomes) was conducted to treat CD44+/CD133+ SKOV3 and CoC1 cells to observe cell growth and stemness. Next, the differentially expressed miRNAs in SKOV3 cells after exosome treatment were filtered using microarray analysis. Subsequently, the cell viability was detected after reducing the exosomal miR-454 and the addition of a Wnt pathway inhibitor C59. Finally, the pro-tumorigenic function of exosomes on OC cells in vivo was investigated. Key findings: After co-culture with 231-derived exosomes, the stemness of CSCs were promoted. Subsequently, the reduction of exosomal miR-454 weakened the roles of exosomes on cell stemness. Proline-rich transmembrane protein 2 (PRRT2) was substantiated as a target gene of miR-454 in SKOV3 and CoC1 cells. C59 reversed the repressive role of exosomes in stemness of CSCs. When being evaluated in a mouse model, exosomal miR-454 led to an efficacious effect in suppressing the tumor weight and volume in vivo. Significance: Altogether, 231-derived exosomes carrying miR-454 disrupted the Wnt pathway by targeting PRRT2, thereby promoting CSC stemness in vitro and OC cell growth in vivo.

Background Acquired resistance to drug involves multilayered genetic and epigenetic regulation. Inhibition of EZH2 has proven to reverse the tamoxifen resistance back to the sensitive state in breast cancer. However, the molecular players involved in EZH2-mediated effects on tamoxifen-resistant MCF-7 cells are unknown. This study was conducted to understand the global change in proteome profile of tamoxifen-resistant MCF-7 breast cancer cells upon EZH2 knockdown. Methods Tamoxifen resistance MCF-7 breast cancer cells were established using increasing concentrations of 4-hydroxy tamoxifen. Using label free proteomics approach, we studied the alteration in total proteome in resistant cells as well as cells transfected with siEZH2 in comparison to sensitive and cells transfected with non-targeting siRNA. Results Here, we report list of proteins that were previously not recognized for their role in tamoxifen resistance and hold a close association with breast cancer patient survival. Proteins Annexin A2, CD44, nucleosome assembly protein 1, and lamin A/C were among the most upregulated protein in tamoxifen-resistant cells that were found to be abrogated upon EZH2 knockdown. The study suggests the involvement for various proteins in acquiring resistance towards tamoxifen and anticipates further research for investigating their therapeutic potentials. Conclusion Overall, we propose that targeting EZH2 or the molecules down the cascade might be helpful in reacquiring sensitivity to tamoxifen in breast cancer.