論文 - 詳細
| RRC ID | 58765 |
|---|---|
| 著者 | Azuma Y, Yokobori T, Mogi A, Yajima T, Kosaka T, Iijima M, Shimizu K, Shirabe K, Kuwano H. |
| タイトル | Cancer exosomal microRNAs from gefitinib-resistant lung cancer cells cause therapeutic resistance in gefitinib-sensitive cells. |
| ジャーナル | Surg Today |
| Abstract |
PURPOSE:Exosomes and their cargo microRNAs play a significant role in various biological processes in cancer. We hypothesized that microRNAs in exosomes secreted by gefitinib-resistant lung cancer cells might induce resistant phenotypes in otherwise gefitinib-sensitive lung cancer cells. METHODS:We isolated exosomes generated by the gefitinib-resistant human lung adenocarcinoma cell line PS-9/ZD. PC-9, which is a gefitinib-sensitive cell line, was treated with the PC-9/ZD exosomes, and these PC-9 cells were analyzed for cell proliferation after treatment with gefitinib. miRNA arrays were analyzed in PC-9 and PC-9/ZD cells, and we isolated microRNAs that were expressed at elevated levels in PC-9/ZD cells. Furthermore, we transfected these microRNAs into PC-9 cells and analyzed the effects on the cells' sensitivity to gefitinib. RESULTS:Exosomes isolated from PC-9/ZD cells significantly increased the proliferation of PC-9 cells during gefitinib treatment. A microRNA array analysis showed that miR-564, miR-658, miR-3652, miR-3126-5p, miR-3682-3p and miR-6810-5p were significantly upregulated in PC-9/ZD cells. PC-9 cells transfected with miR-564 or miR-658 showed chemo-resistant phenotypes. CONCLUSION:Exosomal miR-564 and miR-658 derived from gefitinib-resistant lung cancer cells induce drug resistance in sensitive cells. Cell-to-cell interaction via exosomal microRNAs may be a novel mechanism and therapeutic target of resistance against gefitinib. |
| 巻・号 | 50(9) |
| ページ | 1099-1106 |
| 公開日 | 2020-9-1 |
| DOI | 10.1007/s00595-020-01976-x |
| PII | 10.1007/s00595-020-01976-x |
| PMID | 32052182 |
| MeSH | Adenocarcinoma of Lung / drug therapy* Adenocarcinoma of Lung / genetics* Adenocarcinoma of Lung / pathology Cell Communication / genetics* Cell Line, Tumor Cell Proliferation / drug effects Cell Proliferation / genetics Drug Resistance, Neoplasm / genetics* Exosomes / genetics* Gefitinib / pharmacology* Gefitinib / therapeutic use* Humans Lung Neoplasms / drug therapy* Lung Neoplasms / genetics* Lung Neoplasms / pathology MicroRNAs* / metabolism MicroRNAs* / physiology Molecular Targeted Therapy Up-Regulation |
| IF | 1.878 |
| 引用数 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | PC-9(RCB4455) |