Predictive role of UCA1-containing exosomes in cetuximab-resistant colorectal cancer
| Autor: | Xiaoli Wei, Xiao-Xue Du, Yanjing Li, Shu-lin Jiang, Heng-heng Yuan, Yu Han, Ying-nan Yang, Rui Zhang, Jing-wen Du |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Colorectal cancer medicine.medical_treatment Cetuximab Drug resistance Exosomes lcsh:RC254-282 Targeted therapy 03 medical and health sciences 0302 clinical medicine Genetics medicine lcsh:QH573-671 neoplasms UCA1 Metastatic colorectal cancer lcsh:Cytology business.industry Biomarker lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease digestive system diseases Microvesicles 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer cell Cancer research Biomarker (medicine) Primary Research business Progressive disease medicine.drug |
| Zdroj: | Cancer Cell International, Vol 18, Iss 1, Pp 1-11 (2018) Cancer Cell International |
| ISSN: | 1475-2867 |
| DOI: | 10.1186/s12935-018-0660-6 |
| Popis: | Background Primary or acquired resistance to cetuximab often occurs during targeted therapy in metastatic colorectal cancer (mCRC) patients. In many cancers, the key role of the long noncoding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) in anticancer drug resistance has been confirmed. Emerging evidence has shown that specific exosomal lncRNAs may serve as meaningful biomarkers. In this study, we hypothesize that exosomal UCA1 might predict the response to cetuximab in CRC patients. Methods First, acquired cetuximab-resistant cell lines were generated, and UCA1 expressions in these cells and their exosomes were compared. We also systematically evaluate the stability of exosomal UCA1. Thereafter, the predictive value of exosomal UCA1 in CRC patients treated with cetuximab was evaluated. Finally, through cell apoptosis assays and immunofluorescence staining, we analyzed the role of UCA1-containing exosomes in conferring cetuximab resistance. Results UCA1 expression was markedly higher in cetuximab-resistant cancer cells and their exosomes. Exosomal UCA1 was shown to be detectable and stable in serum from CRC patients. In addition, circulating UCA1-containing exosomes could predict the clinical outcome of cetuximab therapy in CRC patients, and UCA1 expression was considerably higher in the progressive disease/stable disease patients than in the partial response/complete response patients. Furthermore, exosomes derived from cetuximab-resistant cells could alter UCA1 expression and transmit cetuximab resistance to sensitive cells. Conclusions We discovered a novel role of UCA1-containing exosomes, showed their capability to transmit drug resistance and investigated their potential clinical use in predicting cetuximab resistance. |
| Databáze: | OpenAIRE |
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